cholecystokinin and Body-Weight

Gonadal steroids are among the many factors that influence food intake and body weight in mammals. Hormonal effects on these processes are particularly striking in female rats, which show large increases in food intake and body weight after ovariectomy. A key role of estradiol in the control of food intake and energy balance in humans is evidenced by the fact that the incidence of obesity increases greatly after menopause [American College of Obstetricians and Gynecologists. Body mass index and insulin resistance. Obstet Gynecol 2004;104:5s-10]. The actions of estradiol on neural systems that regulate eating may also account in part for sex differences in food intake and eating disorders, which occur much more frequently in young women [Sodersten P, Bergh C. Anorexia nervosa: towards a neurobiologically based therapy. Eur J Pharmacol 2003;480:67-74]. This paper presents a minireview of research examining the changes in feeding that occur during the ovarian cycle, the effects of estradiol withdrawal and replacement on food intake and body weight, and the neurobiological mechanisms by which estradiol influences feeding behavior. A model of hormone action on food intake that emerges from this research views estradiol as an indirect control of eating and meal size, producing changes in feeding behavior by modulating the central processing of both satiating and orexigenic peptides that represent direct controls of eating. Some of the shortcomings of the model and directions for future research are discussed.

Topics: Animals; Body Weight; Cholecystokinin; Eating; Estradiol; Female; Ghrelin; Humans; Male; Ovariectomy; Satiety Response

In recent years, obesity and its associated health disorders and costs have increased. Accumulation of adipose tissue, or fat, in the intra-abdominal adipose depot is associated with an increased risk of developing cardiovascular problems, type-2 diabetes mellitus, certain cancers, and other disorders like the metabolic syndrome. Males and females differ in terms of how and where their body fat is stored, in their hormonal secretions, and in their neural responses to signals regulating weight and body fat distribution. Men and post-menopausal women accumulate more fat in their intra-abdominal depots than pre-menopausal women, resulting in a greater risk of developing complications associated with obesity. The goal of this review is to discuss the current literature on sexual dimorphisms in body weight regulation, adipose tissue accrual and deposition.

Topics: Adiposity; Animals; Body Fat Distribution; Body Weight; Cholecystokinin; Eating; Estradiol; Female; Ghrelin; Humans; Hypothalamic Hormones; Insulin; Leptin; Male; Melanins; Mice; Neuropeptide Y; Pituitary Hormones; Rats; Receptors, Estrogen; Serotonin; Sex Characteristics

Energy balance of the body is determined mainly by the function of various hypothalamic and brainstem nuclei, according to a complex interaction between the regulation of body temperature (actual metabolic rate vs. heat loss) and regulation of body weight (metabolic rate vs. food intake). The direct effect of central anabolic neuropeptides (neuropeptide Y, orexins, melanin concentrating hormone, etc.) is to enhance food intake and suppress metabolic rate with a tendency to cause hypothermia, while central catabolic neuropeptides (melanocortins, corticotropin releasing factor, cocaine-amphetamine regulated peptide, etc.) suppress food intake and enhance energy expenditure with a tendency to induce hyperthermia. Many other neuropeptides are neither clearly anabolic, nor clearly catabolic, but still influence these complex hypothalamic/brainstem functions. Some peripheral peptides (e.g. leptin, insulin, ghrelin) acting at either peripheral or cerebral sites also contribute to the regulation of energy balance. The prevailing thermoregulatory status, the substances or neural signals representing actual feeding vs. established nutritional states, and the aging process may modify the expression and/or activity of peripheral and central peptides and peptide receptors.

Topics: Adiponectin; Aging; Animals; Body Temperature Regulation; Body Weight; Cholecystokinin; Eating; Energy Metabolism; Female; Ghrelin; Humans; Hypothalamic Hormones; Insulin; Intracellular Signaling Peptides and Proteins; Leptin; Male; Melanins; Melanocortins; Neuropeptides; Orexins; Peptides; Pituitary Hormones; Signal Transduction

A variety of circulating signals provide essential information to the central nervous system (CNS) regarding nutritional status. The gastrointestinal system produces many such molecules that are now known to have profound effects on feeding behavior and the control of metabolism as a consequence of their ability to regulate the neural circuitry involved in metabolic homeostasis. Although many of these substances have been suggested to directly access such brain centers, their lipophobic characteristics suggest that alternative mechanisms should be considered. In this paper, we consider one such alternative, namely, that a specialized group of CNS structures collectively known as the sensory circumventricular organs (CVOs), which are not protected by the normal blood-brain barrier, may play important roles in such blood to brain communications. Specifically, we review a developing literature that shows receptors for, and functional actions of, gastrointestinal hormones such as amylin, cholecystokinin, ghrelin and peptide YY in the area postrema and subfornical organ. Collectively, these observations suggest potentially significant roles for the sensory CVOs in the regulation of energy balance.

Topics: Adipokines; Appetite Regulation; Area Postrema; Blood-Brain Barrier; Body Weight; Cholecystokinin; Energy Metabolism; Feeding Behavior; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Homeostasis; Humans; Neurons; Peptide Hormones; Peptide YY; Satiation; Signal Transduction; Subfornical Organ

The prevalence of obesity has reached epidemic proportions worldwide and the incidence of overweight and obesity continues to rise. Diet plays a significant role in the modulation of body weight and there is some evidence to suggest that calcium or dairy intake may modulate body weight and body fat mass. Several mechanisms through which calcium or dairy products may affect body weight or fat have been suggested, including a possible effect on appetite and food intake. A recent study investigated to what extent people could compensate for increased energy intake from dairy products and found that a 7-day increase in dairy intake had no effect on appetite and no evidence of complete compensation for the raised energy intake. In another study, the effects of altered calcium content of a dairy-based test meal was evaluated in obese subjects; the findings indicated that although a higher calcium content of the meal reduced the extent of post-prandial chylomicron-associated triglyceridemia, there was no effect on appetite-related hormones (CCK, ghrelin, GLP-1, or PPY) or on energy intake from a subsequent ad libitum test meal. Thus, this new evidence does not support the hypothesis that high calcium or dairy intake reduces appetite or food intake.

Topics: Appetite; Body Fat Distribution; Body Weight; Calcium, Dietary; Cholecystokinin; Dairy Products; Eating; Energy Intake; Humans; Randomized Controlled Trials as Topic

An understanding of the mechanisms that regulate energy homeostasis is essential for understanding novel obesity therapies. The status of energy reserves is communicated to the brain by adiposity and satiety signals. These signals modify either anabolic or catabolic pathways and, consequently, alter food intake in line with signaled energy requirements. New antiobesity therapies are in development that target anabolic or catabolic regulatory networks to reduce food intake and/or increase energy expenditure to promote weight loss.

Topics: Adiposity; Animals; Anti-Obesity Agents; Body Weight; Cannabinoid Receptor Modulators; Cholecystokinin; Energy Metabolism; Glucagon-Like Peptide 1; Humans; Leptin; Melanocyte-Stimulating Hormones; Neuropeptide Y; Obesity; Pro-Opiomelanocortin; Receptor, Cannabinoid, CB1; Serotonin; Serotonin Receptor Agonists; Thyroid Hormones

The significant burden of overweight and obesity on our society necessitates the development of lifestyle strategies that facilitate successful long-term body weight management. Recently, the discovery of novel cellular modulators of the brain-gut axis have generated much interest in possible therapeutic manipulation of these and other hormones that regulate energy intake. These modulators include the enterohormones ghrelin, peptide YY 3-36, and cholecystokinin, and the adipocyte-derived hormone leptin. There is some evidence that dietary macronutrient composition can influence concentrations of these hormones, which could impact sensations of hunger, satiety, and ultimately energy intake. The purpose of this review is to provide background information on these four peripheral hormones involved in energy intake regulation, to discuss what is currently known about their mechanism of action, and to present research findings related to the effect of macronutrient composition on concentrations and efficacy of these hormones. Potential applications of this information are also discussed.

Topics: Body Weight; Brain; Cholecystokinin; Eating; Energy Intake; Energy Metabolism; Feeding Behavior; Gene Expression Regulation; Ghrelin; Humans; Leptin; Peptide Fragments; Peptide Hormones; Peptide YY

Summary Cholecystokinin (CCK), a peptide that is distributed widely throughout the gastrointestinal tract and the central nervous system, has a number of physiological effects including the stimulation of gallbladder contraction and pancreatic and gastric acid secretion, slowing of gastric emptying and suppression of energy intake. This review focuses on current knowledge relating to (i) the effects of CCK on energy intake; (ii) the role for CCK in the pathophysiology of obesity; and (iii) the therapeutic potential for strategies which modulate the action or secretion of CCK in the management of obesity. While CCK plays a role in the acute regulation of appetite and energy intake, there is little evidence to suggest that specific CCK receptor agonists, or modulation of the actions of endogenous CCK by dietary manipulation, have sustainable inhibitory effects on energy intake. Hence, it appears unlikely that manipulating the pathways by which CCK modulates energy intake will prove to be an effective strategy in the long term management of obesity.

Topics: Animals; Appetite; Body Weight; Cholecystokinin; Digestive System Physiological Phenomena; Energy Intake; Gastrointestinal Hormones; Hormone Antagonists; Humans; Obesity; Proglumide; Receptors, Cholecystokinin

Obesity has reached epidemic levels in industrialized countries and is increasing worldwide. This trend has serious public health consequences, since obesity increases the risk of diabetes, hypertension, heart disease, sleep apnea, cancer, arthritis, cholelithiasis, fatty liver disease, and other complications. Obesity is the result of an imbalance between energy intake and expenditure; hence, an understanding of how gastrointestinal function is integrated with the hormonal regulation of energy balance is pertinent to the pathophysiology of obesity. Nutrients, peptides, and neural afferents from the gut influence the size and frequency of meals and satiety. The long-term regulation of energy stores is mediated primarily through the actions of adiposity hormones, such as leptin and insulin, in the hypothalamus and other neuronal circuits in the brain. Efforts are underway to determine how these peripheral and central pathways may be targeted for treatment of obesity and related diseases.

Topics: Animals; Appetite; Body Weight; Cholecystokinin; Energy Metabolism; Gastrointestinal Hormones; Ghrelin; Humans; Insulin; Leptin; Obesity; Peptide Hormones; Peptide YY; Peptides; Satiety Response; Stomach

Humans in many countries are currently experiencing what has been called an epidemic of obesity. That is, the average body weight (and amount of fat stored in the body) is increasing over years, carrying with it a multitude of associated medical, psychological, and economic problems. While there is no shortage of possible causes of this epidemic, increased availability and consumption of high-fat (HF), calorically dense and generally quite palatable food is often touted as a likely culprit. In order to better assess the impact of consuming a diet with those qualities, we have developed a well-controlled animal model in which the effects of chronic consumption of a high-fat diet can be dissociated from those of becoming obese per se. Long-Evans rats are fed one of two semipurified pelleted diets, a HF diet that contains 20% fat by weight and a low-fat (LF) diet that contains 4% fat by weight. Pair-fed animals consume the HF diet but are limited to the daily caloric intake of LF rats. Another group receives pelleted chow. Relative to animals consuming diets low in fat, HF animals weigh more, have more carcass fat, are hyperinsulinemic and hyperleptinemic, and are insulin resistant. HF-fed animals, independent of whether they become obese or not, also have central insulin and MTII insensitivity. Finally, HF rats have a down-regulated hypothalamic apo A-IV system that could contribute to their hyperphagia.

Topics: Animals; Body Weight; Cholecystokinin; Dietary Fats; Disease Models, Animal; Energy Intake; Energy Metabolism; Homeostasis; Humans; Insulin; Obesity; Rats; Time Factors

Topics: Animals; Body Weight; Carrier Proteins; Cholecystokinin; Humans; Intracellular Signaling Peptides and Proteins; Leptin; Nerve Tissue Proteins; Neuropeptide Y; Neuropeptides; Orexins; Pro-Opiomelanocortin; Reproduction

The present review of the satiating effect of cholecystokinin in humans has revealed that cholecystokinin is a physiological satiety factor in humans. The results demonstrate the efficacy of the satiating actions of exogenous and endogenous CCK in humans. The therapeutic potential of CCK analogues cannot be estimated until further studies are performed that demonstrate the efficacy of CCK analogues for decreasing body weight, and the safety of CCK when administered repetitively for prolonged periods.

Topics: Animals; Appetite; Body Weight; Cholecystokinin; Feeding and Eating Disorders; Feeding Behavior; Gastric Mucosa; Humans

Leptin administered (either intracerebroventricularly, icv, or intraperitoneally, ip) acts in synergy with CCK to suppress food intake and body weight in lean mice or rats. The potentiating effect induced by the co-injection of ip CCK and leptin to inhibit food consumption in mice is mediated by the CCK-A receptor and capsaicin sensitive afferents. In vitro, studies in rats showed that a subset of gastric vagal afferent fibers responded to leptin injected directly into the gastric artery only after a prior intra-arterial CCK injection. Moreover, the tonic activity of gastric-related neurons in the nucleus tractus solitarius (NTS) increased when leptin was delivered into the gastric chamber of an in vitro stomach-brainstem preparation. CCK co-injected with leptin potentiated Fos expression selectively in the area postrema, NTS and paraventricular nucleus of the hypothalamus (PVN), which points to the PVN as part of the afferent and efferent limbs of the circuitry involved in the synergistic interaction between leptin and CCK. The dampening of CCK or leptin inhibitory action on ingestive behavior when either factor is not present or their receptors are non functional supports the notion that such leptin-CCK interaction may have a physiological relevance. These observations provide a mean through which leptin and CCK integrate short- and mid-term meal-related input signals into long-term control of energy balance.

Topics: Animals; Body Weight; Cholecystokinin; Drug Synergism; Eating; Humans; Leptin; Mice; Rats

Evidence that CCK participates in the control of meal size is compelling, but the avenues by which CCK may affect daily food intake and body weight regulation are still uncertain. Although participation of brain CCK in control of food intake is acknowledged, our focus here is on participation of peripheral CCK in the control of food intake. Therefore, in this article we (1) review evidence for CCK's participation in control of meal size, (2) document involvement of CCK-A receptors located on vagal sensory neurons in control of food intake by exogenous and endogenous CCK, (3) point out apparent discrepancies in the experimental record, which auger for non-endocrine sources of CCK and non-vagal sites of CCK action, and (4) summarize recent observations, suggesting mechanisms by which CCK could participate in the control of daily food intake and body weight regulation.

Topics: Animals; Body Weight; Cholecystokinin; Eating; Humans

The six major research advances in metabolic and hormonal controls of food intake that have altered the direction or have broadened the scope of the field in the last 25 years are discussed. The advances selected are: (1) GI processes and meal termination-the CCK pathway; (2) Brain insulin hypothesis; (3) Glucose-dependent processes in periphery, plasma, and brain including the transient declines in blood glucose signaling meal initiation; (4) Fatty acid oxidation in the liver; (5) Behavioral and metabolic patterns; and (6) New pathways from molecular genetics and molecular biology-the OB protein pathway.

Topics: Animals; Blood Glucose; Body Weight; Brain; Cholecystokinin; Eating; Fatty Acids; Humans; Insulin; Lipid Peroxidation; Liver

Topics: Animals; Body Weight; Bombesin; Cholecystokinin; Eating; Gastrointestinal Hormones; Glucagon; Humans; Insulin; Lipid Metabolism; Neuropeptides; Receptors, Bombesin

Obesity: a bio-behavioural-environmental phenomenon: Obesity is on the increase all over the world in technologically advanced countries, developing countries and rural communities. What is causing this upward drift in body weight? Can drugs do anything to ameliorate the situation? It is generally agreed that obesity results from genetic vulnerability combined with a provocative environmental situation. This provides the basis for a psychobiological interaction in which behaviour plays a key role. This is the case since it is behaviour which translates biological propensities into action on the environment, and it is behaviour which mediates (in part) the effect of the environment upon biology. Two particularly important behavioural aspects of the genes-environment interaction are low levels of physical activity (high sedentariness) and dietary habits which favour overconsumption (high intake of energy, particularly as fat). One continuing theme of research is the development of drugs to allow people to gain control over appetite by modifying eating patterns (dietary habits) through a number of possible mechanisms. The use of drugs to make people more willing or more able to engage in physical activity is not widely discussed although the use of drugs to increase total energy expenditure (via a variety of mechanisms) is actively researched. More than a decade ago Sullivan defined the framework for the development of anti-obesity drugs by specifying that drugs could act on energy intake, energy output or on those mechanisms involved in the assimilation and storage of lipids in the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Body Weight; Cholecystokinin; Feeding Behavior; Forecasting; Humans; Obesity; Serotonin Receptor Agonists; Sympathomimetics

Regulation of food intake is commonly treated as a negative feedback-loop. Hunger and/or appetite lead man and animals to ingest food. The subsequent meal-contingent activation of pre- and postabsorptive mechanisms then leads to satiety. The activation of oral and gastrointestinal chemo- and mechanoreceptors is important on the preabsorptive site. The gastrointestinal hormone cholecystokinin may also have a physiological satiety effect. Preabsorptive satiety mechanisms are influenced by the rate of gastrointestinal transit. The pancreatic hormone glucagon, which is released during meal taking, and various metabolites contribute to the postabsorptive regulation of food intake through activation of hepatic chemoreceptors, which are connected to the brain via predominantly vagal afferents. In addition, glucoreceptors in the brain, in particular in the nucleus of the solitary tract, contribute to food intake regulation by monitoring blood glucose concentration or, more specifically, glucose utilization. The nucleus of the solitary tract, which relays vagal afferents from gut and liver and also gustatory afferents, projects to the hypothalamus and to other forebrain structures. In this neural network the informations from the periphery are integrated by various neurotransmitters and neuropeptides, but the exact role of the substances involved is not fully understood yet. Body weight and, hence, body fat presumably affects feeding through modulation of a postabsorptive mechanism.

Topics: Animals; Body Weight; Chemoreceptor Cells; Cholecystokinin; Eating; Glucagon; Glucose; Humans; Mechanoreceptors; Satiation

Topics: Animals; Appetite; Body Weight; Cholecystokinin; Endorphins; Feeding Behavior; Humans; Models, Biological; Neuropeptides; Satiation; Taste

This report juxtaposes findings from weanling rats with precise lesions in the ventromedial (VMNL rats) to data of weanling rats with lesions in the dorsomedial (DMNL) hypothalamic nuclei. Despite the proximity of the two nuclei their destruction produces opposite effects in most cases but similar responses in other parameters. Absolute and relative food intake are normal in VMNL rats yet they become obese in the face of normal body weight gains. DMNL rats show both reduced absolute food intake and body weight but normal relative food intake and body composition. Both VMNL and DMNL cause reduced linear growth and running wheel activity. DMNL rats defend their lower body weight set point against various challenges and maintain normal body composition. Organ growth in both absolute and relative terms is reduced in VMNL rats. In DMNL rats relative organ growth is normal. Pancreatic growth, protein/pancreas and content and concentrations of several pancreatic enzymes are normal in DMNL but reduced in VMNL rats. Mean 24-hour plasma growth hormone (GH) and corticosterone (B) levels are reduced and insulin levels are greatly elevated in VMNL rats; prolactin (PRL) levels are normal. In DMNL rats, GH, B, insulin and somatomedin activity are normal but PRL is elevated. Circadian rhythms of GH, insulin and triiodothyronine are normal in DMNL rats but B levels are disrupted, as they are in VMNL rats. Glucose incorporation and oxidation in adipose tissue of VMNL rats are enhanced in VMNL rats but normal in DMNL rats. Gluconeogenesis in VMNL rats is enhanced as early as 4 hours post-operatively; in DMNL rats it is normal at this time and several weeks thereafter. Basal lipolysis in epididymal fat pads is elevated in both VMNL and DMNL rats but epinephrine-stimulated lipolysis is elevated in VMNL and decreased in DMNL rats. Both VMNL and DMNL rats show normal basal and epinephrine-stimulated lipolysis in interscapular brown adipose tissue. Several hepatic enzymes are normal in DMNL and depressed in VMNL rats. The above data suggest that the DMN and its circuitry are part of an "organismic" set point system with a "true" body weight and no fat set point, as seems to be the case in the VMNL rat.

Topics: Animal Population Groups; Animals; Animals, Suckling; Basal Metabolism; Body Weight; Cholecystokinin; Circadian Rhythm; Corticosterone; Dorsomedial Hypothalamic Nucleus; Feeding Behavior; Gluconeogenesis; Glucose; Growth Hormone; Hypothalamus, Middle; Insulin; Lipolysis; Liver; Narcotics; Neurotransmitter Agents; Prolactin; Rats; Self Administration; Syndrome; Time Factors; Triiodothyronine; Ventromedial Hypothalamic Nucleus

Topics: Animals; Anorexia Nervosa; Autonomic Nervous System; Body Weight; Brain; Cholecystokinin; Eating; Feeding Behavior; Gastric Emptying; Homeostasis; Humans; Hunger; Hypothalamus; Insulin; Intestinal Absorption; Liver; Obesity; Receptor, Insulin; Satiation; Thirst

The physiological controls of feeding behavior in pigs are reviewed. Feeding patterns, central nervous system integration of the control systems and the influence of taste and olfaction are briefly considered, but the emphasis of the review is on the specific control systems that determine meal size. The glucostatic mechanism of stimulation of eating operates in the pig, but is probably an emergency control in response to a severe deficiency of glucose available to the central nervous system. The effective controls determining meal size are predominantly inhibitory signals initiated within or near the gastrointestinal tract by the presence of food. There is evidence that a rise in osmoconcentration caused by the arrival of foodstuffs in the duodenum during a meal can inhibit feeding behavior to a degree proportional to the hypertonicity of the duodenal content. Arrival of chyme in the duodenum will also trigger the release of cholecystokinin (CCK). Exogenous CCK injected by various routes inhibits feeding, suggesting that endogenous CCK acts as a satiety or inhibitory signal during meals. Gastrointestinal distention during meals probably also acts as an inhibitory signal, but only preliminary studies have been made to delineate the role of this factor in feeding behavior. It is concluded that although considerable research has been conducted to reveal what control mechanisms operate in pigs, even the mechanisms already investigated are not firmly established as operating in normal meals. The osmoreceptive, CCK and gastrointestinal distention control systems are promising hypotheses worthy of further study, and the search for other control systems that may also participate continues.

Topics: Animals; Body Weight; Central Nervous System; Cholecystokinin; Digestive System Physiological Phenomena; Drinking Behavior; Duodenum; Feeding Behavior; Glucose; Hypothalamus; Insulin; Satiation; Smell; Swine; Taste; Temperature

There are now a large number of experiments demonstrating that peripheral administration of exogenous cholecystokinin or its synthetic analogue, CCK-8, reduces meal size in a number of species. The peptide interacts with other factors which influence satiety, and treatments thought to be effective in eliciting secretion of cholecystokinin have predictable effects on meal size. Cholecystokinin is effective in the genetically obese Zucker rat, obese rats with lesions of the ventromedial hypothalamus, and subdiaphragmatically vagotomized rats. Somatostatin and bombesin are also reasonable candidates for satiety factors. Intraperitoneal naloxone reduces meal size in rats, and beta-endorphin injected intraventricularly causes an increase in meal size of 50% over 30 minutes. We conclude that cholecystokinin and bombesin may interact in weight regulation and control of meal time food intake.

Topics: Appetite; Body Weight; Cholecystokinin; Eating; Humans; Peptides; Satiety Response

Topics: Body Weight; Cholecystokinin; Digestion; Digestive System Physiological Phenomena; Gastric Juice; Gastric Mucosa; Gastrins; Gastrointestinal Hormones; Gastrointestinal Motility; Glucagon; Humans; Hydrogen-Ion Concentration; Insulin; Pancreas; Pepsin A; Peptides; Secretin

Strong compensatory responses, with reduced resting metabolic rate (RMR), increased exercise efficiency (ExEff) and appetite, are activated when weight loss (WL) is achieved with continuous energy restriction (CER), which try to restore energy balance. Intermittent energy restriction (IER), where short spells of energy restriction are interspaced by periods of habitual energy intake, may offer some protection in minimizing those responses. We aimed to compare the effect of IER versus CER on body composition and the compensatory responses induced by WL.. Changes in body weight (≈12.5% WL) and composition were similar in both groups. Fasting RQ and ExEff at 10 W increased in both groups. Losing weight, either by IER or CER dieting, did not induce significant changes in subjective appetite ratings. RMR decreased and ExEff at 25 and 50 W increased (P < 0.001 for all) in IER group only. Basal and postprandial AG increased (P < 0.05) in IER group, whereas basal active GLP-1 decreased (P = 0.033) in CER group only. Postprandial CCK decreased in both groups (P = 0.0012 and P = 0.009 for IER and CER groups, respectively). No between group differences were apparent for any of the outcomes.. The technique used to achieve energy restriction, whether it is continuous or intermittent, does not appear to modulate the compensatory mechanisms activated by weight loss.. NCT02169778 (the study was registered in clinicaltrial.gov).

Topics: Adult; Basal Metabolism; Body Composition; Body Weight; Caloric Restriction; Cholecystokinin; Diet, Reducing; Eating; Energy Intake; Exercise; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Middle Aged; Norway; Obesity; Oxygen Consumption; Peptide YY; Weight Loss

Whey protein (WP), when consumed in small amounts prior to a meal, improves post-meal glycemic control more than can be explained by insulin-dependent mechanisms alone. The objective of the study was to identify the mechanism of action of WP beyond insulin on the reduction of post-meal glycemia. In a randomized crossover study, healthy young men received preloads (300 ml) of WP (10 and 20 g), glucose (10 and 20 g) or water (control). Paracetamol (1.5 g) was added to the preloads to measure gastric emptying. Plasma concentrations of paracetamol, glucose, and β-cell and gastrointestinal hormones were measured before preloads (baseline) and at intervals before (0-30 min) and after (50-230 min) a preset pizza meal (12 kcal/kg). Whey protein slowed pre-meal gastric emptying rate compared to the control and 10 g glucose (P<.0001), and induced lower pre-meal insulin and C-peptide than the glucose preloads (P<.0001). Glucose, but not WP, increased pre-meal plasma glucose concentrations (P<.0001). Both WP and glucose reduced post-meal glycemia (P=.0006) and resulted in similar CCK, amylin, ghrelin and GIP responses (P<.05). However, compared with glucose, WP resulted in higher post-meal GLP-1 and peptide tyrosine-tyrosine (PYY) and lower insulin concentrations, without altering insulin secretion and extraction rates. For the total duration of this study (0-230 min), WP resulted in lower mean plasma glucose, insulin and C-peptide, but higher GLP-1 and PYY concentrations than the glucose preloads. In conclusion, pre-meal consumption of WP lowers post-meal glycemia by both insulin-dependent and insulin-independent mechanisms.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Cholecystokinin; Cross-Over Studies; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Insulin; Islet Amyloid Polypeptide; Male; Milk Proteins; Peptide YY; Whey Proteins; Young Adult

After weight loss, changes in the circulating levels of several peripheral hormones involved in the homeostatic regulation of body weight occur. Whether these changes are transient or persist over time may be important for an understanding of the reasons behind the high rate of weight regain after diet-induced weight loss.. We enrolled 50 overweight or obese patients without diabetes in a 10-week weight-loss program for which a very-low-energy diet was prescribed. At baseline (before weight loss), at 10 weeks (after program completion), and at 62 weeks, we examined circulating levels of leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin and subjective ratings of appetite.. Weight loss (mean [±SE], 13.5±0.5 kg) led to significant reductions in levels of leptin, peptide YY, cholecystokinin, insulin (P<0.001 for all comparisons), and amylin (P=0.002) and to increases in levels of ghrelin (P<0.001), gastric inhibitory polypeptide (P=0.004), and pancreatic polypeptide (P=0.008). There was also a significant increase in subjective appetite (P<0.001). One year after the initial weight loss, there were still significant differences from baseline in the mean levels of leptin (P<0.001), peptide YY (P<0.001), cholecystokinin (P=0.04), insulin (P=0.01), ghrelin (P<0.001), gastric inhibitory polypeptide (P<0.001), and pancreatic polypeptide (P=0.002), as well as hunger (P<0.001).. One year after initial weight reduction, levels of the circulating mediators of appetite that encourage weight regain after diet-induced weight loss do not revert to the levels recorded before weight loss. Long-term strategies to counteract this change may be needed to prevent obesity relapse. (Funded by the National Health and Medical Research Council and others; ClinicalTrials.gov number, NCT00870259.).

Topics: Body Mass Index; Body Weight; Cholecystokinin; Diet, Reducing; Female; Gastrointestinal Hormones; Ghrelin; Glucagon-Like Peptide 1; Humans; Intention to Treat Analysis; Leptin; Male; Middle Aged; Obesity; Peptide YY; Peptides; Postmenopause; Weight Loss

To assess weight maintenance after weight loss by consumption of yoghurt with a novel fat emulsion (Olibra) including effects on body composition, resting energy expenditure (REE), fat oxidation, hunger feelings and satiety hormones.. A randomized, placebo-controlled, double-blind, parallel design. A 6-week weight loss period (2.1 MJ/day) was followed by 18 weeks weight maintenance with test (Olibra) or placebo yoghurt.. Fifty overweight women (age: 18-58 years, body mass index (BMI) 25-32 kg/m2).. In weeks 1, 7 and 25, a satiety test with questionnaires and blood samples for analysis of satiety hormones. In weeks 2, 8 and 26, REE, body weight and body composition.. During weight maintenance after significant body weight reduction, there was no significant increase in body weight in the test group (1.1+/-3.4 kg); the placebo group did gain weight (3.0+/-3.1 kg, P<0.001). Compared to the placebo group, the test group was less hungry 4 h after yoghurt consumption in week 25 (P<0.05) and showed increased glucagon like peptide-1 values 180 min after yoghurt consumption (week 25 vs week 1, P<0.05). Measured REE as a function of fat-free mass (FFM) was significantly higher than predicted REE (P<0.05) in week 26 for the test group, but not for the placebo group. Fat mass (FM) was significantly more decreased in the test group (6.5+/-4.1 kg) compared to the placebo group (4.1+/-3.6 kg) (week 26 vs week 2, P<0.05).. Consumption of Olibra yoghurt improved weight maintenance compared to placebo, which can be explained by the relatively higher REE as a function of FFM, relatively higher decrease in FM and the relatively lower increase in hunger.

Topics: Adolescent; Adult; Appetite Depressants; Body Mass Index; Body Weight; Caloric Restriction; Cholecystokinin; Dietary Supplements; Double-Blind Method; Emulsions; Energy Metabolism; Fats; Female; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Middle Aged; Obesity; Overweight; Peptide Hormones; Satiety Response; Weight Gain; Weight Loss; Yogurt

Negative feedback regulation of pancreatic proteases controls pancreatic secretion in most species and pancreatic growth in rodents. Its mechanism involves the inhibition of intraluminal proteases, resulting in sustained elevation of plasma cholecystokinin (CCK) concentrations, producing a chronic trophic stimulus to the pancreas that leads to the formation of pancreatic nodules and adenomas. Ximelagatran, whose active form, melagatran, inhibits both thrombin and the serine protease trypsin, is under clinical development as an oral anticoagulant. Recent data indicate species differences in the expression of CCK receptor subtypes in the pancreas. CCK1 receptors are abundant in rat pancreas but are either absent or present at very low levels in human pancreas. As part of the clinical studies, we examined whether long-term ximelagatran administration causes CCK release and exerts possible trophic effects on the pancreas in humans.. One hundred thirty patients requiring anticoagulation treatment for atrial fibrillation randomly received, in a double-blind fashion, either 36 mg oral ximelagatran twice daily or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0. Before enrollment and after 12 months of treatment, computed tomography scans of the pancreas were performed, and pancreas volumes were quantified using the summation-of-areas technique. Three months after the initiation of drug treatment, plasma CCK concentrations were measured by radioimmunoassay 120 minutes after the patients drank 240 mL of a mixed liquid meal (Ensure).. After 3 months of treatment, plasma CCK concentrations did not differ between the ximelagatran and warfarin groups, 15 +/- 18 and 11 +/- 17 pmol/L (X +/- SD; P = 0.22), respectively. The initial average pancreas volumes were 82 +/- 31 and 88 +/- 28 mL in the ximelagatran and warfarin groups, respectively, and decreased to 70 +/- 25 and 75 +/- 28 mL, respectively, after 12 months of treatment. Although the decrease in pancreas volume with time was significant in each group (P = 0.0001), the magnitude of the volume reduction was similar in the 2 groups.. In contrast to rats, in which long-term oral administration of ximelagatran stimulates pancreatic growth and adenoma formation, in humans, ximelagatran does not increase plasma CCK concentrations and has no demonstrable trophic effect on the human pancreas.

Topics: Aged; Anticoagulants; Atrial Fibrillation; Azetidines; Benzylamines; Body Mass Index; Body Weight; Cholecystokinin; Double-Blind Method; Humans; Pancreas; Tomography, X-Ray Computed; Warfarin

Although dietary protein produces higher acute satiety relative to carbohydrate, the influence of protein source and body mass index (BMI) has not been clearly described.. The objective of the study was to assess postprandial responses to different protein sources, compared with glucose, in males with normal and high BMI.. This was a randomized, crossover study of four preloads followed by blood sampling (+15, 30, 45, 60, 90, 120, 180 min) and buffet meal.. The study was conducted at an outpatient clinic.. The study population included 72 men, with a BMI range 20.6-39.9 kg/m(2).. Interventions consisted of liquid preloads (1.1 MJ, 450 ml) containing 50 g whey, soy, gluten, or glucose.. Fasting and postprandial plasma glucose, insulin, ghrelin, glucagon-like peptide-1 (GLP-1) and cholecystokinin (n = 38), ad libitum energy intake, and appetite ratings were measured.. Energy intake was 10% lower after all protein preloads, compared with the glucose treatment (P < 0.05), independent of BMI status and protein type. All protein loads prolonged the postprandial suppression of ghrelin (P < 0.01) and elevation of GLP-1 (P < 0.01) and cholecystokinin (P < 0.05). Fasting GLP-1 concentrations [overweight, 17.5 +/- 1.3; lean, 14.7 +/- 0.1 pg/ml (5.2 +/- 0.4 and 4.4 +/- 0.1 pmol/liter, respectively); P < 0.001] and postprandial responses (P = 0.038) were higher in overweight subjects.. Whey, soy, and gluten similarly tend to reduce ad libitum food intake 3 h later in lean and overweight males relative to glucose. Postprandial ghrelin, GLP-1, insulin, and cholecystokinin may contribute to this higher satiety after protein consumption. GLP-1 concentrations are increased in overweight subjects, which may affect satiety responses in this group.

Topics: Adult; Aged; Appetite Regulation; Blood Glucose; Body Mass Index; Body Weight; Cholecystokinin; Cross-Over Studies; Dietary Proteins; Eating; Energy Intake; Ghrelin; Glucagon-Like Peptide 1; Glutens; Hormones; Humans; Insulin; Kinetics; Male; Middle Aged; Milk Proteins; Obesity; Peptide Hormones; Regression Analysis; Satiation; Soybean Proteins; Whey Proteins

Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction.. To study whether orlistat, by lipase inhibition, impairs gall-bladder emptying, thus further predisposing weight-losing obese subjects to gallstone formation.. Patients entering a randomized clinical trial of 1 month of diet, followed by treatment with placebo, 3 x 60 mg orlistat or 3 x 120 mg orlistat, underwent gall-bladder emptying studies measured by ultrasound. Meal-induced cholecystokinin release and gall-bladder emptying were investigated at the start, at randomization and after 1 and 12 months.. One month of dieting did not change gall-bladder emptying and cholecystokinin release. After 1 month, placebo treatment resulted in a decreased fasting volume of 11%, compared with increases of 26% and 47% with 60 and 120 mg orlistat, respectively. Gall-bladder emptying increased by 9% with placebo and decreased by 15% and 53% with 60 and 120 mg orlistat, respectively. Fasting cholecystokinin values and cholecystokinin release decreased significantly in the orlistat group. After 1 year, a persistent but attenuated effect of orlistat on gall-bladder emptying and cholecystokinin release remained. Three of 40 patients developed gallstones, two on placebo with major weight loss and one on 60 mg orlistat.. One month of lipase inhibition by orlistat significantly impaired gall-bladder motility, which persisted to some extent after 1 year. Obese subjects with diabetes or hyperlipidaemia, who are more at risk of gallstones, should be followed carefully.

Topics: Adult; Anti-Obesity Agents; Body Weight; Cholecystokinin; Female; Gallbladder; Humans; Lactones; Lipase; Male; Middle Aged; Obesity; Orlistat; Weight Loss

The lipase inhibitor, orlistat, is used in the treatment of obesity and reduces fat absorption by about 30%. However, the mean weight loss induced by orlistat is less than expected for the degree of fat malabsorption. It was hypothesised that lipase inhibition with orlistat attenuates the suppressive effects of oral fat on subsequent energy intake in normal-weight subjects. Fourteen healthy, lean subjects (nine males, five females; aged 25 +/- 1.3 years) were studied twice, in a double-blind fashion. The subjects received a high-fat yoghurt 'preload' (males 400 g (2562 kJ); females 300 g (1923 kJ)), containing orlistat (120 mg) on one study day (and no orlistat on the other 'control' day), 30 min before ad libitum access to food and drinks; energy intake was assessed during the following 8 h. Blood samples were taken at regular intervals for the measurement of plasma cholecystokinin (CCK). Each subject performed a 3 d faecal fat collection following each study. Energy intake during the day was greater following orlistat (10,220 (SEM 928) kJ) v. control (9405 (SEM 824) kJ) (P=0.02). On both days plasma CCK increased (P<0.05) after the preload. Plasma CCK 20 min following ingestion of the preload was less after orlistat (4.1 (SEM 0.9) pmol/l) v. control (5.3 (SEM 0.9) pmol/l (P=0.028); however there was no difference in the area under the curve 0-510 min between the two study days. Fat excretion was greater following orlistat (1017 (SEM 168) kJ) v. control (484 (SEM 90) kJ) (P=0.004). In conclusion, in healthy, lean subjects the acute inhibitory effect of fat on subsequent energy intake is attenuated by orlistat and the increase in energy intake approximates the energy lost due to fat malabsorption.

Topics: Adult; Appetite; Body Weight; Cholecystokinin; Dietary Fats; Double-Blind Method; Eating; Energy Metabolism; Enzyme Inhibitors; Feces; Female; Humans; Lactones; Lipase; Male; Orlistat

Six of eight obese men ate significantly less food during an intravenous infusion of the C-terminal octapeptide of cholecystokinin (CCK-8, 4 ng . kg-1 . min-1) than during a saline infusion in a double blind experimental paradigm. Subjects stopped eating sooner during CCK-8. CCK-8 did not change the rate of eating. No overt side effects were reported or observed. This is the first report of the satiety effect of CCK-8 in obese humans and it suggests that the therapeutic potential of CCK-8 for the treatment of obesity deserves investigation.

Topics: Body Weight; Cholecystokinin; Eating; Energy Intake; Humans; Male; Obesity; Peptide Fragments; Sincalide

Metabolic programming may be induced by reduction or enhancement of litter size, which lead to neonatal over or undernutrition, respectively. Changes in neonatal nutrition can challenge some regulatory processes in adulthood, such as the hypophagic effect of cholecystokinin (CCK). In order to investigate the effects of nutritional programming on the anorexigenic function of CCK in adulthood, pups were raised in small (SL, 3 pups per dam), normal (NL, 10 pups per dam), or large litters (LL, 16 pups per dam), and on postnatal day 60, male rats were treated with vehicle or CCK (10 µg/Kg) for the evaluation of food intake and c-Fos expression in the area postrema (AP), nucleus of solitary tract (NTS), and paraventricular (PVN), arcuate (ARC), ventromedial (VMH), and dorsomedial (DMH) nuclei of the hypothalamus. Overnourished rats showed increased body weight gain that was inversely correlated with neuronal activation of PaPo, VMH, and DMH neurons, whereas undernourished rats had lower body weight gain, inversely correlated with increased neuronal activation of PaPo only. SL rats showed no anorexigenic response and lower neuron activation in the NTS and PVN induced by CCK. LL exhibited preserved hypophagia and neuron activation in the AP, NTS, and PVN in response to CCK. CCK showed no effect in c-Fos immunoreactivity in the ARC, VMH, and DMH in any litter. These results indicate that anorexigenic actions, associated with neuron activation in the NTS and PVN, induced by CCK were impaired by neonatal overnutrition. However, these responses were not disrupted by neonatal undernutrition. Thus, data suggest that an excess or poor supply of nutrients during lactation display divergent effects on programming CCK satiation signaling in male adult rats.

Topics: Animals; Body Weight; Cholecystokinin; Eating; Hypothalamus; Male; Malnutrition; Neurons; Overnutrition; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Rats, Wistar; Solitary Nucleus

To evaluate whether the potent hypophagic and weight-suppressive effects of growth differentiation factor-15 (GDF15) and semaglutide combined would be a more efficacious antiobesity treatment than either treatment alone by examining whether the neural and behavioural mechanisms contributing to their anorectic effects were common or disparate.. Three mechanisms were investigated to determine how GDF15 and semaglutide induce anorexia: the potentiation of the intake suppression by gastrointestinal satiation signals; the reduction in motivation to feed; and the induction of visceral malaise. We then compared the effects of short-term, combined GDF15 and semaglutide treatment on weight loss to the individual treatments. Rat pharmaco-behavioural experiments assessed whether GDF15 or semaglutide added to the satiating effects of orally gavaged food and exogenous cholecystokinin (CCK). A progressive ratio operant paradigm was used to examine whether GDF15 or semaglutide reduced feeding motivation. Pica behaviour (ie, kaolin intake) and conditioned affective food aversion testing were used to evaluate visceral malaise. Additionally, fibre photometry studies were conducted in agouti-related protein (AgRP)-Cre mice to examine whether GDF15 or semaglutide, alone or in combination with CCK, modulate calcium signalling in hypothalamic AgRP neurons.. Semaglutide reduced food intake by amplifying the feeding-inhibitory effect of CCK or ingested food, inhibited the activity of AgRP neurons when combined with CCK, reduced feeding motivation and induced malaise. GDF15 induced visceral malaise but, strikingly, did not affect feeding motivation, the satiating effect of ingested food or CCK signal processing. Combined GDF15 and semaglutide treatment produced greater food intake and body weight suppression than did either treatment alone, without enhancing malaise.. GDF15 and semaglutide reduce food intake and body weight through largely distinct processes that produce greater weight loss and feeding suppression when combined.

Topics: Agouti-Related Protein; Animals; Anorexia; Body Weight; Cholecystokinin; Eating; Glucagon-Like Peptides; Growth Differentiation Factor 15; Mice; Rats; Weight Loss

Cholecystokinin cholescintigraphy is used clinically to quantify gallbladder ejection fraction as an indicator of functional gallbladder disorder. It can also provide the opportunity to quantify an individual's responsiveness to the physiologic stimulant of gallbladder contraction, cholecystokinin, which is a major regulator of appetite and postprandial satiety.

Topics: Adult; Aged; Body Weight; Cholecystokinin; Cholelithiasis; Cholesterol; Female; Gallbladder; Gallbladder Emptying; Humans; Indicators and Reagents; Kinetics; Male; Middle Aged; Protein Binding; Radionuclide Imaging; Receptors, Cell Surface; Sensitivity and Specificity

Excluding the foregut (distal stomach and duodenum) from food transit in RYGB normalizes glucose tolerance. Excluding/removing the duodenal mucosa partly improves glycemic control. So far, the effect of excluding/removing the gastric mucosa remains unknown.. To observe the effect of removing the distal gastric mucosa on glucose tolerance.. Thirty fatty Sprague-Dawley rats received low-dose streptozotocin (STZ) to induce type 2 diabetes (T2D), then randomly assigned to Roux-en-Y gastric bypass (RYGB, n = 8), distal gastric mucosa removal (DGMR, n = 8), duodenal-jejunal bypass (DJB, n = 8), and Sham (n = 6) groups. In the DGMR group, the distal third of the gastric mucosa was removed by thermal ablation using an electrocautery. Rats were followed for 8 weeks postoperatively. Preoperative oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and mixed-meal tolerance test (MMTT) were repeated 3 and 6 weeks postoperatively. Changes in body weight, food intake, and fasting blood glucose were also recorded.. Gastrin AUC decreased significantly (p < 0.05) in the DGMR group after surgery. A significantly increased GLP-1 AUC was found in the RYGB, DGMR, and DJB groups at week 3 and only the RYGB group at week 6 postoperatively. The improved glucose tolerance in the RYGB group was significantly greater than the improved glucose tolerance in the DGMR and DJB groups. The improved glucose tolerance 3 and 6 weeks after surgery in the DGMR group was significantly greater than the improved glucose tolerance in the DJB group. Body weight decreased significantly in the RYGB, DGMR, and DJB groups postoperatively.. Removing the distal gastric mucosa induced significant weight loss and improved glycemic control in T2D SD rat model. Therefore, the gastric mucosa exclusion in RYGB may be key to the weight loss and diabetes remission, which perhaps warrants a new theory.

Topics: Animals; Area Under Curve; Bile Acids and Salts; Blood Glucose; Body Weight; C-Reactive Protein; Cholecystokinin; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Fasting; Feeding Behavior; Gastric Bypass; Gastric Mucosa; Glucose Tolerance Test; Glycemic Control; Insulin; Male; Rats, Sprague-Dawley; Weight Loss

To compare appetite markers in reduced-obese individuals with a nonobese control group.. A total of 34 adults with obesity who lost 17% body weight at week 13 and maintained this weight loss (WL) at 1 year were compared with 33 nonobese controls matched for body composition. Basal and postprandial subjective appetite ratings and appetite-related hormone concentrations (ghrelin, total peptide YY, peptide YY3-36, total and active glucagon-like peptide 1, and cholecystokinin) were measured in all participants and repeated at week 13 and 1 year in the weight-reduced group.. WL led to a reduction in prospective food consumption and an increase in feelings of hunger, fullness, and ghrelin secretion (basal and postprandial), but these new ratings were no different from those seen in controls. Postprandial concentrations of active glucagon-like peptide 1, total peptide YY, and cholecystokinin were lower in individuals with obesity at all time points compared with controls.. The increased drive to eat (both subjective feelings of hunger and ghrelin concentrations) seen in reduced-obese individuals, both after acute and sustained WL, reflects a normalization toward a lower body weight. Overall, WL does not have a sustained negative impact on satiety peptide secretion, despite a blunted secretion in individuals with obesity compared with nonobese controls.

Topics: Adult; Appetite; Body Mass Index; Body Weight; Cholecystokinin; Eating; Female; Ghrelin; Glucagon-Like Peptide 1; Homeostasis; Humans; Male; Middle Aged; Obesity; Peptide YY; Satiation; Weight Loss

Cholecystokinin (CCK) is a regulator of appetite and energy intake in man. The aim of this study was to determine the effect of NN9056, a long-acting CCK-1 receptor-selective CCK analogue, on food intake and body weight (BW) in obese Göttingen Minipigs.. Tolerability of NN9056 and acute effects on food intake, pancreas histology, amylase and lipase levels were assessed in lean domestic pigs in doses up to 100 nmol/kg (n = 3-4). Subsequently, obese Göttingen Minipigs were treated subcutaneously (s.c.) once daily for 13 weeks with vehicle, NN9056 low dose (regulated from 5 to 2 nmol/kg) or NN9056 high dose (10 nmol/kg) (n = 7-8). Food intake was measured daily and BW twice weekly. At the end of the treatment period, an intravenous glucose tolerance test (IVGTT) and a 24-h exposure profile was obtained. Data are mean ± SD.. The acute studies in domestic pigs showed significant and dose-dependent effect of NN9056 on food intake, acceptable tolerability and no histopathological signs of pancreatitis. Sub-chronic treatment in obese Göttingen Minipigs was also well tolerated and accumulated food intake was significantly lower in both treated groups compared to vehicle, with no significant difference between the dose levels of NN9056 (41.8 ± 12.6, 51.5 ± 13.8 and 86.5 ± 19.5 kg in high-dose, low-dose and vehicle groups, respectively, p = 0.012 and p < 0.0001 for low and high dose vs. vehicle, respectively). Accordingly, there was a weight loss in both treated groups vs. a weight gain in the vehicle group (-7.2 ± 4.6%, -2.3 ± 3.2% and 12.3 ± 3.9% in the high-dose, low-dose and vehicle groups, respectively, p < 0.0001 for both vs. vehicle). IVGTT data were not significantly different between groups.. NN9056, a long-acting CCK-1 receptor-selective CCK analogue, significantly reduced food intake and BW in obese Göttingen Minipigs after once daily s.c. dosing for 13 weeks.

Topics: Animals; Body Weight; Cholecystokinin; Disease Models, Animal; Eating; Energy Intake; Female; Humans; Obesity; Protein Binding; Swine; Swine, Miniature

The neuropeptide oxytocin is best known for its role during parturition and the milk-let down reflex. Recent evidence identifies a role for oxytocin in eating behaviour. After oxytocin administration, caloric intake is reduced with stronger inhibitory effects in individuals with obesity. Whether the experience of visual food cues affects secretion or circulating levels of oxytocin is unknown. This pilot study had three aims: 1) to measure fasting appetite hormones with a focus on plasma oxytocin concentrations; 2) determine whether healthy vs. hyperpalatable visual food cues differentially altered plasma oxytocin; and 3) assess whether appetite hormone responses to healthy vs. hyperpalatable food images depended on weight or food addiction status. Eighteen healthy women of varying weight status, with/without self-reported food addiction were recruited. Study participants completed a set of standardised questionnaires, including Yale Food Addiction Scale, and attended a one-off experimental session. Blood was collected before and after viewing two sets of food images (healthy and hyperpalatable foods). Participants were randomly allocated in a crossover design to view either healthy images or hyperpalatable foods first. A positive correlation between BMI and plasma oxytocin was found (r

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Case-Control Studies; Cholecystokinin; Cues; Female; Food Addiction; Humans; Middle Aged; Oxytocin; Photic Stimulation; Pilot Projects; Young Adult

The expression of Trim33 (Tif1γ) increases in skeletal muscles during regeneration and decreases upon maturation. Although Trim33 is required for the normal development of other tissues, its role in skeletal muscle is unknown. The current study aimed to define the role of Trim33 in muscle development and regeneration. We generated mice with muscle-specific conditional knockout of Trim33 by combining floxed Trim33 and Cre recombinase under the Pax7 promoter. Muscle regeneration was induced by injuring mouse muscles with cardiotoxin. We studied the consequences of Trim33 knockdown on viability, body weight, skeletal muscle histology, muscle regeneration, and gene expression. We also studied the effect of Trim33 silencing in satellite cells and the C2C12 mouse muscle cell line. Although Trim33 knockdown mice weighed less than control mice, their skeletal muscles were histologically unremarkable and regenerated normally following injury. Unexpectedly, RNAseq analysis revealed dramatically increased expression of cholecystokinin (CCK) in regenerating muscle from Trim33 knockout mice, satellite cells from Trim33 knockout mice, and C2C12 cells treated with Trim33 siRNA. Trim33 knockdown had no demonstrable effect on muscle differentiation or regeneration. However, Trim33 knockdown induced CCK expression in muscle, suggesting that suppression of CCK expression requires Trim33.

Topics: Animals; Body Weight; Cardiotoxins; Cell Survival; Cholecystokinin; Exons; Female; Genotype; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Regeneration; RNA-Seq; Satellite Cells, Skeletal Muscle; Transcription Factors; Transcriptome

The effects on the enteroendocrine system of three different grape seed proanthocyanidin extract (GSPE) treatments are analyzed in rats on a cafeteria diet for 17 weeks.. GSPE is administered in a corrective manner (15 last days of the cafeteria diet) at two doses, 100 and 500 mg GSPE per kg bw. A third, longer treatment in which GSPE (500 mg kg. GSPE modulates the enteroendocrine system in models in which it also reduces food intake or body weight.

Topics: Animals; Body Weight; Cholecystokinin; Diet; Energy Intake; Enteroendocrine Cells; Fatty Acids, Volatile; Female; Ghrelin; Glucagon-Like Peptide 1; Grape Seed Extract; Proanthocyanidins; Rats

High-protein diet (HPD) curtails obesity and/or fat mass, but it is unknown whether it reverses neuroinflammation or alters glucose levels, CCK sensitivity, and gut microbiome in rats fed a Western diet (WD)-induced obesity (DIO). Male rats fed a WD (high fat and sugar) for 12 wk were switched to a HPD for 6 wk. Body composition, food intake, meal pattern, sensitivity to intraperitoneal CCK-8S, blood glucose, brain signaling, and cecal microbiota were assessed. When compared with a normal diet, WD increased body weight (9.3%) and fat mass (73.4%). CCK-8S (1.8 or 5.2 nmol/kg) did not alter food intake and meal pattern in DIO rats. Switching to a HPD for 6 wk reduced fat mass (15.7%) with a nonsignificantly reduced body weight gain, normalized blood glucose, and decreased feeding after CCK-8S. DIO rats on the WD or switched to a HPD showed comparable microbial diversity. However, in HPD versus WD rats, there was enrichment of 114 operational taxonomic units (OTUs) and depletion of 188 OTUs. Of those,

Topics: Animals; Blood Glucose; Body Composition; Body Weight; Brain; Cecum; Cholecystokinin; Cytokines; Diet, Western; Dietary Proteins; Eating; Encephalitis; Male; Microbiota; Obesity; Rats; Rats, Sprague-Dawley

Apolipoprotein AIV (ApoAIV) and cholecystokinin (CCK) are well-known satiating signals that are stimulated by fat consumption. Peripheral ApoAIV and CCK interact to prolong satiating signals. In the present study, we hypothesized that ApoAIV and CCK control energy homeostasis in response to high-fat diet feeding. To test this hypothesis, energy homeostasis in ApoAIV and CCK double knockout (ApoAIV/CCK-KO), ApoAIV knockout (ApoAIV-KO), and CCK knockout (CCK-KO) mice were monitored. When animals were maintained on a low-fat diet, ApoAIV/CCK-KO, ApoAIV-KO, and CCK-KO mice had comparable energy intake and expenditure, body weight, fat mass, fat absorption, and plasma parameters relative to the controls. In contrast, these KO mice exhibited impaired lipid transport to epididymal fat pads in response to intraduodenal infusion of dietary lipids. Furthermore, ApoAIV-KO mice had upregulated levels of CCK receptor 2 (CCK2R) in the small intestine while ApoAIV/CCK-KO mice had upregulated levels of CCK2R in the brown adipose tissue. After 20 wk of a high-fat diet, ApoAIV-KO and CCK-KO mice had comparable body weight and fat mass, as well as lower energy expenditure at some time points. However, ApoAIV/CCK-KO mice exhibited reduced body weight and adiposity relative to wild-type mice, despite having normal food intake. Furthermore, ApoAIV/CCK-KO mice displayed normal fat absorption and locomotor activity, as well as enhanced energy expenditure. These observations suggest that mice lacking ApoAIV and CCK have reduced body weight and adiposity, possibly due to impaired lipid transport and elevated energy expenditure.

Topics: Adiposity; Animals; Apolipoproteins A; Body Weight; Cholecystokinin; Diet, Fat-Restricted; Dietary Fats; Eating; Energy Intake; Energy Metabolism; Homeostasis; Mice, Knockout

Cholecystokinin (CCK) is expressed in cardiomyocytes and may also play an important role in cardiovascular regulation. Clinical studies have shown that plasma CCK levels are an independent marker of cardiovascular mortality in cardiac disease. However, whether the development of postinfarction heart failure is associated with changes in CCK expression is unknown.. To investigate CCK expression patterns and the association between CCK expression and heart functional parameters, we randomized male Sprague-Dawley rats into myocardial infarction (MI) or sham operation (SO) groups. CCK expression levels were assessed by western blotting, immunohistochemistry, real-time polymerase chain reaction (PCR), and enzyme-linked immunosorbent assay (ELISA) at different time points (2, 4 or 6 weeks) after surgery. Brain natriuretic peptide (BNP) concentrations were determined using Western blotting and ELISA, myocardial morphology was assessed by microscopy.. Plasma CCK and BNP levels were significantly increased in all the MI groups compared with the corresponding SO groups. However, the degree to which myocardial CCK mRNA and protein expression levels were increased the MI groups compared with the SO groups was greater in the 4- and 6-week groups than in the 2-week group. Furthermore, plasma CCK levels were positively correlated with BNP concentrations and left ventricular end-systolic diameter (LVDs) and significantly negatively correlated with the ejection fraction (EF) and shortening fraction (SF) in model animals.. Heart failure progression after infarction is associated with upregulated CCK levels; thus, CCK may be useful as a novel marker of heart failure.

Topics: Animals; Biomarkers; Body Weight; Cholecystokinin; Disease Models, Animal; Echocardiography; Enzyme-Linked Immunosorbent Assay; Fibrosis; Heart; Heart Failure; Immunohistochemistry; Male; Myocardial Infarction; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

Endocrine factors released from the central nervous system, gastrointestinal tract, adipose tissue and other peripheral organs mediate the regulation of food intake. Although many studies have evaluated the effect of fed-to-starved transition on the expression of appetite-related genes, little is known about how the expression of appetite-regulating peptides is regulated by the macronutrient composition of the diet. The aim of the present study was to examine the effect of diet composition and nutritional status on the expression of four peptides involved in food intake control in gilthead sea bream (Sparus aurata): neuropeptide Y (NPY), ghrelin, cholecystokinin (CCK) and leptin. Quantitative real-time RT-PCR showed that high protein/low carbohydrate diets stimulated the expression of CCK and ghrelin in the intestine and leptin in the adipose tissue, while downregulation of ghrelin and NPY mRNA levels was observed in the brain. Opposite effects were found for the expression of the four genes in fish fed low protein/high carbohydrate diets or after long-term starvation. Our findings indicate that the expression pattern of appetite-regulating peptides, particularly CCK and ghrelin, is modulated by the nutritional status and diet composition in S. aurata.

Topics: Animals; Body Composition; Body Weight; Cholecystokinin; Diet; Gene Expression Regulation; Ghrelin; Leptin; Linear Models; Neuropeptide Y; RNA, Messenger; Sea Bream; Starvation

We hypothesized that exogenous gastrin releasing peptide-29 (GRP-29), cholecystokinin-8 (CCK-8) and their combination reduce body weight (BW). To test this hypothesis, BW was measured in four groups of diet-induced obese (DIO) male rats infused in the aorta (close to the junctions of the celiac and cranial mesenteric arteries) with saline, CCK-8 (0.5 nmol/kg), GRP-29 (0.5 nmol/kg) and CCK-8+GRP-29 (0.5 nmol/kg each) once daily for a total of 23 days. We found that CCK-8, GRP-29 and CCK-8+GRP-29 reduce BW relative to saline control. In conclusion, CCK-8, GRP-29 and their combination reduce BW in the DIO rat model. If infused near their gastrointestinal sites of action CCK-8, GRP-29 and their combination may have a role in regulating BW.

Topics: Animals; Body Weight; Cholecystokinin; Diet; Drug Therapy, Combination; Gastrin-Releasing Peptide; Gastrointestinal Agents; Infusions, Parenteral; Male; Obesity; Peptide Fragments; Rats; Weight Loss

(1) The objective of this study is to analyze differences in smell-taste capacity between females in extreme weight/eating conditions (EWC) and (2) to explore the interaction between smell/taste capacity, gastric hormones, eating behavior and body mass index (BMI). The sample comprised 239 females in EWC [64 Anorexia nervosa (AN) and 80 age-matched healthy-weight controls, and 59 obese and 36 age-matched healthy-weight controls]. Smell and taste assessments were performed through "Sniffin' Sticks" and "Taste Strips," respectively. The assessment measures included the eating disorders inventory-2, the symptom check list 90-revised, and The Dutch Eating Behavior Questionnaire, as well as peptides from the gastrointestinal tract [Ghrelin, peptide YY, cholecystokinin]. Smell capacity was differentially associated across EWC groups. Smell was clearly impaired in obese participants and increased in AN (hyposmia in Obesity was 54.3 and 6.4 % in AN), but taste capacity did not vary across EWC. Ghrelin levels were significantly decreased in obese subjects and were related to smell impairment. EWC individuals showed a distinct smell profile and circulating ghrelin levels compared to controls. Smell capacity and ghrelin may act as moderators of emotional eating and BMI.

Topics: Adolescent; Adult; Anorexia Nervosa; Body Weight; Cholecystokinin; Feeding Behavior; Female; Ghrelin; Humans; Middle Aged; Obesity; Olfaction Disorders; Peptide YY; Smell; Taste; Taste Disorders; Young Adult

Consumption of sugar-sweetened beverages is associated with overweight and obesity. In this study, we hypothesized that obesity-prone (OP) mice fed a high-fat high-sucrose diet (HFHS) are more sensitive to consumption of sucrose-sweetened water (SSW) than obesity-resistant (OR) mice. After 3weeks of ad libitum access to the HFHS diet (7.5h/day), 180 male mice were classified as either OP (upper quartile of body weight gain, 5.2±0.1g, n=45) or OR (lower quartile, 3.2±0.1g, n=45). OP and OR mice were subsequently divided into 3 subgroups that had access to HFHS (7.5h/day) for 16weeks, supplemented with: i) water (OP/water and OR/water); ii) water and SSW (12.6% w/v), available for 2h/day randomly when access to HFHS was available and for 5 randomly-chosen days/week (OP/SSW and OR/SSW); or iii) water and SSW for 8weeks, then only water for 8weeks (OP/SSW-water and OR/SSW-water). OR/SSW mice decreased their food intake compared to OR/water mice, while OP/SSW mice exhibited an increase in food and total energy intake compared to OP/water mice. OP/SSW mice also gained more body weight and fat mass than OP/water mice, showed an increase in liver triglycerides and developed insulin resistance. These effects were fully reversed in OP/SSW-water mice. In the gut, OR/SSW mice, but not OP/SSW mice, had an increase GLP-1 and CCK response to a liquid meal compared to mice drinking only water. OP/SSW mice had a decreased expression of melanocortin receptor 4 in the hypothalamus and increased expression of delta opioid receptor in the nucleus accumbens compared to OP/water mice when fasted that could explain the hyperphagia in these mice. When access to the sucrose solution was removed for 8weeks, OP mice had increased dopaminergic and opioidergic response to a sucrose solution. Thus, intermittent access to a sucrose solution in mice fed a HFHS diet induces changes in the gut and brain signaling, leading to increased energy intake and adverse metabolic consequences only in mice prone to HFHS-induced obesity.

Topics: Animals; Body Composition; Body Weight; Cholecystokinin; Diet, High-Fat; Disease Models, Animal; Drinking; Eating; Energy Metabolism; Gene Expression Regulation; Glucagon-Like Peptide 1; Glucose Tolerance Test; Hyperphagia; Lipid Peroxidation; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Sucrose; Sweetening Agents

Obestatin is described as an anorexigenic peptide, and has adverse effects of ghrelin. It has no inhibitory effects on acute/chronic food intake, and it has been reported by several researchers. The role of obestatin in metabolism is still not clear. In the present study, the purpose is to determine the effects of chronically administrated obestatin. For this purpose, (1 µmol/kg; i.p.) or ghrelin (1 µmol/kg; i.p.) and food restriction (24h fast:24h fed) on plasma obestatin, ghrelin, leptin, insulin, cholecystokinin (CCK) and glucose levels, and body weight gain were investigated for 14 days in mice. Additionally, mice were treated with acute ip (100 nmol/kg) injections of obestatin or ghrelin to investigate the food consumptions, plasma obestatin and ghrelin levels to determine unknown acute effects of obestatin. Plasma ghrelin levels increased significantly in obestatin administered mice when compared with the control group for chronic treatment. This increase is consistent with immunohistochemical findings which claim that the number of ghrelin and obestatin immunopositive cells in fundus tissue of stomach are considerably high in obestatin treated animals. Plasma obestatin and ghrelin levels has shown an increase endogenously in food restricted mice, but plasma leptin and insulin levels have been found to be lower compared to the control group. Acute administration of obestatin caused a decrease in plasma obestatin level at 60 min after injection and had no effect on the reduction of food intake in each treatment time. These results imply that obestatin may not itself be involved in the metabolism regulation; however, obestatin accompanied by ghrelin may play a role in the long-term regulation of metabolism.

Topics: Animals; Body Weight; Cholecystokinin; Eating; Gene Expression Regulation; Ghrelin; Injections; Insulin; Leptin; Mice; Peptide Hormones

Ingestion of peanuts may have a beneficial effect on weight control, possibly due to the satietogenic action of trypsin inhibitors. The aim of this study was to isolate a new trypsin inhibitor in a typical Brazilian peanut sweet (paçoca) and evaluate its effect in biochemical parameters, weight gain and food intake in male Wistar rats. The trypsin inhibitor in peanut paçoca (AHTI) was isolated. Experimental diets were prepared with AIN-93G supplemented with AHTI. Animals had their weight and food intake monitored. Animals were anesthetized, euthanized, and their bloods collected by cardiac puncture for dosage of cholecystokinin (CCK) and other biochemical parameters. Supplementation with AHTI significantly decreased fasting glucose, body weight gain, and food intake. These effects may be attributed to increased satiety, once supplemented animals showed no evidence of impaired nutritional status and also because AHTI increased CCK production. Thus, our results indicate that AHTI, besides reducing fasting glucose, can reduce weight gain via food intake reduction.

Topics: Animals; Arachis; Blood Glucose; Body Weight; Cholecystokinin; Dietary Supplements; Fasting; Male; Models, Animal; Rats; Rats, Wistar; Trypsin Inhibitors

Several hypotheses for the causes of the obesity epidemic in the US have been proposed. One such hypothesis is that dietary intake patterns have significantly shifted to include unprecedented amounts of refined sugar. We set out to determine if different sugars might promote changes in the hypothalamic mechanisms controlling food intake by measuring several hypothalamic peptides subsequent to overnight access to dilute glucose, sucrose, high fructose corn syrup, or fructose solutions. Rats were given access to food, water and a sugar solution for 24h, after which blood and tissues were collected. Fructose access (as opposed to other sugars that were tested) resulted in a doubling of circulating triglycerides. Glucose consumption resulted in upregulation of 7 satiety-related hypothalamic peptides whereas changes in gene expression were mixed for remaining sugars. Also, following multiple verification assays, 6 satiety related peptides were verified as being affected by sugar intake. These data provide evidence that not all sugars are equally effective in affecting the control of intake.

Topics: Animals; Appetite Regulation; Blood Glucose; Body Weight; Cholecystokinin; Corticotropin-Releasing Hormone; Dietary Sucrose; Eating; Fructose; Glucose; Growth Hormone; High Fructose Corn Syrup; Hypothalamus; Insulin; Male; Rats, Sprague-Dawley; Receptor Activity-Modifying Protein 3; Thyrotropin-Releasing Hormone; Triglycerides; Tumor Necrosis Factor-alpha

"Black" pigment gallstones form in sterile gallbladder bile in the presence of excess bilirubin conjugates ("hyperbilirubinbilia") from ineffective erythropoiesis, hemolysis, or induced enterohepatic cycling (EHC) of unconjugated bilirubin. Impaired gallbladder motility is a less well-studied risk factor. We evaluated the spontaneous occurrence of gallstones in adult germfree (GF) and conventionally housed specific pathogen-free (SPF) Swiss Webster (SW) mice. GF SW mice were more likely to have gallstones than SPF SW mice, with 75% and 23% prevalence, respectively. In GF SW mice, gallstones were observed predominately in heavier, older females. Gallbladders of GF SW mice were markedly enlarged, contained sterile black gallstones composed of calcium bilirubinate and <1% cholesterol, and had low-grade inflammation, edema, and epithelial hyperplasia. Hemograms were normal, but serum cholesterol was elevated in GF compared with SPF SW mice, and serum glucose levels were positively related to increasing age. Aged GF and SPF SW mice had deficits in gallbladder smooth muscle activity. In response to cholecystokinin (CCK), gallbladders of fasted GF SW mice showed impaired emptying (females: 29%; males: 1% emptying), whereas SPF SW females and males emptied 89% and 53% of volume, respectively. Bilirubin secretion rates of GF SW mice were not greater than SPF SW mice, repudiating an induced EHC. Gallstones likely developed in GF SW mice because of gallbladder hypomotility, enabled by features of GF physiology, including decreased intestinal CCK concentration and delayed intestinal transit, as well as an apparent genetic predisposition of the SW stock. GF SW mice may provide a valuable model to study gallbladder stasis as a cause of black pigment gallstones.

Topics: Age Factors; Animals; Bile Pigments; Body Weight; Calcium; Cholecystokinin; Female; Gallbladder; Gallstones; Genetic Predisposition to Disease; Germ-Free Life; Hydrogen-Ion Concentration; Logistic Models; Male; Mice; Muscle Contraction; Muscle, Smooth; Risk Factors; Sex Factors; Species Specificity; Time Factors

Intake of sodas has been shown to increase energy intake and to contribute to obesity in humans and in animal models, although the magnitude and importance of these effects are still debated. Moreover, intake of sugar sweetened beverages is often associated with high-fat food consumption in humans. We studied two different accesses to a sucrose-sweetened water (SSW, 12.3%, a concentration similar to that usually found in sugar sweetened beverages) in C57BL/6 mice fed a normal-fat (NF) or a high-fat (HF) diet in a scheduled access (7.5h). NF-fed and HF-fed mice received during 5weeks access to water, to SSW continuously for 7.5h (SSW), or to water plus SSW for 2h (randomly-chosen time slot for only 5 random days/week) (SSW-2h). Mouse preference for SSW was greater in HF-fed mice than NF-fed mice. Continuous SSW access induced weight gain whatever the diet and led to greater caloric intake than mice drinking water in NF-fed mice and in the first three weeks in HF-fed mice. In HF-fed mice, 2h-intermittent access to SSW induced a greater body weight gain than mice drinking water, and led to hyperphagia on the HF diet when SSW was accessible compared to days without SSW 2h-access (leading to greater overall caloric intake), possibly through inactivation of the anorexigenic neuropeptide POMC in the hypothalamus. This was not observed in NF-fed mice, but 2h-intermittent access to SSW stimulated the expression of dopamine, opioid and endocannabinoid receptors in the nucleus accumbens compared to water-access. In conclusion, in mice, a sucrose solution provided 2h-intermittently and a high-fat diet have combined effects on peripheral and central homeostatic systems involved in food intake regulation, a finding which has significant implications for human obesity.

Topics: Animals; Body Composition; Body Weight; Brain; Cholecystokinin; Diet, High-Fat; Drinking Behavior; Eating; Energy Intake; Feeding Behavior; Food Deprivation; Gene Expression Regulation; Ghrelin; Leptin; Male; Mice; Mice, Inbred C57BL; Peptide YY; Sucrose; Sweetening Agents; Time Factors

We have previously demonstrated that a number of rats fed a moderately high-fat diet (MHFD) become obese and hypertensive and had compromised sympathoinhibitory and vasodilator responses to the gut hormones cholecystokinin (CCK) and gastric leptin. This has implications for increased resistance in vascular beds that attract a large proportion of cardiac output after a meal and may be an important mechanism underlying the development of hypertension in obesity in which food consumption is greatly increased. The aim of this study was to determine whether swapping a MHFD for a low-fat diet (LFD) would induce weight loss in obese animals, reverse the signs of hypertension and restore sympathoinhibitory reflexes. Male Sprague-Dawley rats were placed on a LFD (controls; n = 8) or a MHFD (n = 24) for 11 weeks after which the latter displayed either an obesity-prone (OP) or obesity-resistant (OR) phenotype. All animals were fed a LFD for a further 6 weeks after which they were anaesthetised with isoflurane and artificially ventilated for evaluation of resting arterial pressure (AP) and renal sympathetic nerve responses to CCK (0.1-4 μg/kg) and leptin (15 μg/kg). Weight gain in OP animals remained higher than OR or controls following diet switch (P < 0.05 for both). Resting AP was not significantly different between OP (103 ± 4 mmHg), OR (102 ± 3 mmHg) or control (104 ± 3 mmHg) animals and sympathoinhibitory responses to CCK or leptin were not different between the groups (P > 0.05). These results demonstrate that diet modification can have beneficial effects on sympathetic function and restore normotension without the need for weight reduction.

Topics: Animals; Arterial Pressure; Autonomic Agents; Body Weight; Cholecystokinin; Diet, Fat-Restricted; Diet, High-Fat; Disease Models, Animal; Gastrointestinal Agents; Genetic Predisposition to Disease; Hypertension; Leptin; Male; Obesity; Rats, Sprague-Dawley; Sympathetic Nervous System

Seeds are excellent sources of proteinase inhibitors, some of which may have satietogenic and slimming actions. We evaluated the effect of a trypsin inhibitor from Tamarindus indica L. seeds on weight gain, food consumption and cholecystokinin levels in Wistar rats.. A trypsin inhibitor from Tamarindus was isolated using ammonium sulfate (30-60%) following precipitation with acetone and was further isolated with Trypsin-Sepharose affinity chromatography. Analyses were conducted to assess the in vivo digestibility, food intake, body weight evolution and cholecystokinin levels in Wistar rats. Histological analyses of organs and biochemical analyses of sera were performed.. The trypsin inhibitor from Tamarindus reduced food consumption, thereby reducing weight gain. The in vivo true digestibility was not significantly different between the control and Tamarindus trypsin inhibitor-treated groups. The trypsin inhibitor from Tamarindus did not cause alterations in biochemical parameters or liver, stomach, intestine or pancreas histology. Rats treated with the trypsin inhibitor showed significantly elevated cholecystokinin levels compared with animals receiving casein or water.. The results indicate that the isolated trypsin inhibitor from Tamarindus reduces weight gain by reducing food consumption, an effect that may be mediated by increased cholecystokinin. Thus, the potential use of this trypsin inhibitor in obesity prevention and/or treatment should be evaluated.

Topics: Animals; Body Weight; Cholecystokinin; Digestion; Eating; Gastrointestinal Tract; Male; Models, Animal; Obesity; Phytotherapy; Plant Extracts; Rats, Wistar; Satiation; Seeds; Tamarindus; Trypsin Inhibitors; Weight Gain

Hyperemesis gravidarum (HG) is described as unexplained excessive nausea and vomiting during pregnancy. Some gut hormones that regulate appetite may have important role in etiopathogenesis of HG and weight changes during pregnancy. In this study, levels of gut satiety hormones were evaluated in pregnant women with HG.. This prospective case-control study was conducted in 30 women with HG and 30 healthy pregnant women without symptoms of HG. Fasting venous blood samples were taken from all subjects for measurement of plasma gut hormone levels; obestatin (pg/mL), peptide YY (PYY), pancreatic polypeptide (PP) and cholecystokinin (CCK).. Plasma PYY and PP levels were significantly higher in HG group. The most important parameter in diagnosis of HG was plasma PP level. Simple use of PP level led to the diagnosis 91.1 % of HG cases correctly. The single most important parameter in the prediction of HG was also PP level.. Anorexigenic gut hormones might have important role in etiopathogenesis of hyperemesis gravidarum and weight changes during pregnancy.

Topics: Adult; Body Weight; Case-Control Studies; Cholecystokinin; Fasting; Female; Ghrelin; Humans; Hyperemesis Gravidarum; Pancreatic Polypeptide; Peptide YY; Pregnancy; Prospective Studies; Weight Gain; Young Adult

Cholecystokinin (CCK) is released in response to lipid feeding and regulates pancreatic digestive enzymes vital to the absorption of nutrients. Our previous reports demonstrated that cholecystokinin knockout (CCK-KO) mice fed for 10 weeks of HFD had reduced body fat mass, but comparable glucose uptake by white adipose tissues and skeletal muscles. We hypothesized that CCK is involved in energy homeostasis and lipid transport from the small intestine to tissues in response to acute treatment with dietary lipids. CCK-KO mice with comparable fat absorption had increased energy expenditure and were resistant to HFD-induced obesity. Using intraduodenal infusion of butter fat and intravenous infusion using Liposyn III, we determined the mechanism of lipid transport from the small intestine to deposition in lymph and adipocytes in CCK-KO mice. CCK-KO mice had delayed secretion of Apo B48-chylomicrons, lipid transport to the lymphatic system, and triglyceride (TG)-derived fatty acid uptake by epididymal fat in response to acute treatment of intraduodenal lipids. In contrast, CCK-KO mice had comparable TG clearance and lipid uptake by white adipocytes in response to TGs in chylomicron-like emulsion. Thus, we concluded that CCK is important for lipid transport and energy expenditure to control body weight in response to dietary lipid feeding.

Topics: Adipocytes; Adipose Tissue; Animals; Apolipoprotein B-48; Body Weight; Cholecystokinin; Chylomicrons; Diet, High-Fat; Dietary Fats; Energy Intake; Energy Metabolism; Intestine, Small; Lipid Metabolism; Liver; Lymphatic System; Male; Mice, Inbred C57BL; Mice, Knockout; Organ Size

Deoxynivalenol (DON), a trichothecene mycotoxin that commonly contaminates cereal grains, is a public health concern because of its adverse effects on the gastrointestinal and immune systems. The objective of this study was to compare effects of DON on anorectic responses in aged (22 mos) and adult (3 mos) mice. Aged mice showed increased feed refusal with both acute i.p. (1 mg/kg and 5 mg/kg) and dietary (1, 2.5, 10 ppm) DON exposure in comparison to adult mice. In addition to greater suppression of food intake from dietary DON exposure, aged mice also exhibited greater but transient body weight suppression. When aged mice were acutely exposed to 1 mg/kg bw DON i.p., aged mice displayed elevated DON and DON3GlcA tissue levels and delayed clearance in comparison with adult mice. Acute DON exposure also elicited higher proinflammatory cytokine and satiety hormone responses in the plasma of the aged group compared with the adult group. Increased susceptibility to DON-induced anorexia in aged mice relative to adult mice suggests that advanced life stage could be a critical component in accurate human risk assessments for DON and other trichothecenes.

Topics: Aging; Animals; Anorexia; Body Weight; Cholecystokinin; Cytokines; Eating; Male; Mice, Inbred C57BL; Peptide YY; Satiety Response; Tissue Distribution; Trichothecenes

Previously, we have identified a novel role for the cytoplasmic protein, synphilin-1(SP1), in the controls of food intake and body weight in both mice and Drosophila. Ubiquitous overexpression of human SP1 in brain neurons in transgenic mice results in hyperphagia expressed as an increase in meal size. However, the mechanisms underlying this action of SP1 remain to be determined. Here we investigate a potential role for altered gut feedback signaling in the effects of SP1 on food intake. We examined responses to peripheral administration of cholecytokinin (CCK), amylin, and the glucagon like peptide-1 (GLP-1) receptor agonist, exendin-4. Intraperitoneal administration of CCK at doses ranging from 1-10 nmol/kg significantly reduced glucose intake in wild type (WT) mice, but failed to affect intake in SP1 transgenic mice. Moreover, there was a significant attenuation of CCK-induced c-Fos expression in the dorsal vagal complex in SP1 transgenic mice. In contrast, WT and SP1 transgenic mice were similarly responsive to both amylin and exendin-4 treatment. These studies demonstrate that SP1 results in a CCK response deficiency that may contribute to the increased meal size and overall hyperphagia in synphillin-1 transgenic mice.

Topics: Animals; Body Weight; Brain; Carrier Proteins; Cholecystokinin; Cytoplasm; Eating; Exenatide; Feeding Behavior; Female; Gene Expression Regulation; Genotype; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hyperphagia; Infusions, Parenteral; Intestinal Mucosa; Intracellular Signaling Peptides and Proteins; Islet Amyloid Polypeptide; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Nerve Tissue Proteins; Neurons; Obesity; Peptides; Proto-Oncogene Proteins c-fos; Signal Transduction; Venoms

Artificial nutrition is frequently associated with hepatobiliary complications, probably due to the inherent derangement of the gastrointestinal tract physiology. Alterations of hepatic lipid metabolism are likely to be involved. The aim of the present study was to investigate the effect of artificial nutrition on bile acid production, a key event in cholesterol homeostasis, in humans.. Eleven patients receiving artificial nutrition, either parenteral nutrition (PN; n = 6) or enteral nutrition (EN; n = 5) with no previous history of liver disease, underwent analysis of cholesterol 7α-hydroxylation rates in vivo, a measure of bile acid formation, by isotope release analysis after intravenous injection of [7α-(3)H]cholesterol. The results were compared with those obtained in a population of 16 age-matched control subjects.. Hydroxylation rates were lower in patients with artificial nutrition (PN: 94 ± 13 mg/d; EN: 230 ± 39 mg/d, mean ± SEM) when compared with controls (385 ± 47 mg/d) (P < .01, 1-way analysis of variance). In a patient receiving EN, hydroxylation rates increased 3.5-fold after treatment with the cholecystokinin analogue ceruletide (20 µg bid for 2 weeks intramuscularly). Serum lathosterol-to-cholesterol ratio, a marker of cholesterol synthesis, was also significantly reduced in artificial nutrition, whereas serum levels of fibroblast growth factor 19 (FGF19) were increased.. In vivo 7α-hydroxylation is suppressed in artificial nutrition, particularly in PN. The finding associates with reduced cholesterol production, possibly as a metabolic consequence. The data suggest a regulatory role of gastrointestinal hormones and FGF19 on bile acid production and might suggest a pathophysiological basis for some common complications of artificial nutrition, such as gallstone disease and cholestasis.

Topics: Administration, Intravenous; Adult; Aged; Bile Acids and Salts; Body Mass Index; Body Weight; Cholecystokinin; Cholesterol; Enteral Nutrition; Female; Fibroblast Growth Factors; Gastrointestinal Hormones; Gastrointestinal Tract; Homeostasis; Humans; Hydroxylation; Linear Models; Lipid Metabolism; Liver; Liver Diseases; Male; Middle Aged; Parenteral Nutrition

The contribution of hypothalamic appetite-regulating peptides to further hyperphagia accompanying the course of lactation in rats was investigated by using PCR array and real-time PCR. Furthermore, changes in the mRNA expression for appetite-regulating peptides in the hypothalamic arcuate nucleus (ARC) were analyzed at all stages of pregnancy and lactation, and also after weaning. Food intake was significantly higher during pregnancy, lactation, and after weaning than during non-lactation periods. During lactation, ARC expression of mRNAs for agouti-related protein (AgRP) and peptide YY was increased, whereas that of mRNAs for proopiomelanocortin (POMC) and cholecystokinin (CCK) was decreased, in comparison with non-lactation periods. The increase in AgRP mRNA expression during lactation was especially marked. The plasma level of leptin was significantly decreased during the course of lactation, whereas that of acyl-ghrelin was unchanged. In addition, food intake was negatively correlated with the plasma leptin level during lactation. This study has clarified synchronous changes in the expression of many appetite-regulating peptides in ARC of rats during lactation. Our results suggest that hyperphagia during lactation in rats is caused by decreases in POMC and CCK expression and increases in AgRP expression in ARC, the latter being most notable. Together with the decrease in the blood leptin level, such changes in mRNA expression may explain the further hyperphagia accompanying the course of lactation.

Topics: Adipose Tissue, White; Agouti-Related Protein; Animals; Appetite; Arcuate Nucleus of Hypothalamus; Body Weight; Cholecystokinin; Eating; Female; Lactation; Leptin; Male; Neuropeptide Y; Neuropeptides; Organ Size; Pregnancy; Pro-Opiomelanocortin; Rats; Rats, Wistar; RNA, Messenger

Dietary chloroplast thylakoids have previously been found to reduce food intake and body weight in animal models, and to change metabolic profiles in humans in mixed-food meal studies. The aim of this study was to investigate the modulatory effects of thylakoids on glucose metabolism and appetite-regulating hormones during an oral glucose tolerance test in pigs fed a high fat diet.. Six pigs were fed a high fat diet (36 energy% fat) for one month before oral glucose tolerance test (1 g/kg d-glucose) was performed. The experiment was designed as a cross-over study, either with or without addition of 0.5 g/kg body weight of thylakoid powder.. The supplementation of thylakoids to the oral glucose tolerance test resulted in decreased blood glucose concentrations during the first hour, increased plasma cholecystokinin concentrations during the first two hours, and decreased late postprandial secretion of ghrelin.. Dietary thylakoids may be a novel agent in reducing the glycaemic responses to high carbohydrate and high glycaemic index foods. Thylakoids may in the future be promising for treatment and prevention of diabetes, overweight and obesity.

Topics: Animals; Appetite; Blood Glucose; Body Weight; Cholecystokinin; Ghrelin; Glucose; Glucose Tolerance Test; Glycemic Index; Intestinal Absorption; Swine; Thylakoids

The effect of body weight status on appetite, glycemic response and gastric emptying rate was investigated using a liquid meal. Lean and overweight males rated their subjective appetite with blood samples collected for measurement of glucose, biomarkers of appetite and gastric emptying rate for 3 h following consumption of the isocaloric test meal. Overweight participants had a higher rating on postprandial hunger (p < 0.001), preoccupation with food (p < 0.001) and desire to eat (p < 0.001), with fullness being lower (p = 0.001). Postprandial plasma concentration of cholecystokinin-33 was lower (p = 0.007) and total ghrelin was higher (p = 0.012) in overweight participants. A delayed gastric emptying rate was observed in lean participants. There was no difference in postprandial glycemic response (p = 0.189). These results suggest the postprandial appetite pattern was different between lean and overweight males when consuming an isocaloric meal. This may have implications for overweight individuals who attempt to lose weight through restricting food intake.

Topics: Adult; Appetite; Blood Glucose; Body Mass Index; Body Weight; Cholecystokinin; Gastric Emptying; Ghrelin; Glycemic Index; Humans; Hunger; Male; Meals; Overweight; Postprandial Period; Thinness; Young Adult

A total of 121 steers (162 ± 3.0 kg BW and 148 ± 2.7 d old) were used to study the effect of dietary energy density and meal size (limiting the amount of concentrate delivered at each feeder visit) on performance, hormones associated with the regulation of intake, and carcass and meat quality. Steers were allocated by BW to 6 pens. Each pen had the same BW mean and CV, and pens were randomly assigned to 3 treatments (2 pens/treatment): a concentrate of moderate energy density (3.23 Mcal ME/kg, 6.2% ether extract) fed for ad libitum intake with no control on meal size (CTR), a concentrate of high-energy density (3.43 Mcal ME/kg, 8.3% ether extract) fed for ad libitum intake with no control on meal size (HE), and the same high-energy concentrate offered for ad libitum intake but with meal size limited to a maximum concentrate delivery of 0.6 kg DM/visit (HELM). Body weight was recorded every 14 d; concentrate consumption and eating pattern were recorded daily. On d 163, blood samples were collected to determine serum concentrations of leptin, ghrelin, glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), glucose, and insulin. After slaughter (on d 166 to 170), the 9-10-11 rib section was removed to estimate separable bone, lean, and fat. Meat quality of LM was analyzed. Data were analyzed using a mixed-effects model with repeated measures. Steers in the HELM treatment had a lower (P < 0.01) final BW and ADG than CTR and HE steers. Concentrate intake was greater (P < 0.001) in CTR (6.6 ± 0.10 kg/d) than in HE steers (5.7 ± 0.10 kg/d), and HELM (5.2 ± 0.10 kg/d) consumed less concentrate than CTR and HE steers. However, HE and HELM steers were more (P < 0.01) efficient than CTR steers. The mean number of daily meals and eating rate were less (P < 0.05) for HELM than for HE or CTR. At d 163, serum concentrations of GLP-1, CCK, and insulin were lower (P < 0.05), and leptin (P = 0.10) and glucose (P = 0.08) concentrations tended to be lower for HELM than for CTR or HE. Carcass conformation and HCW were less (P < 0.05) for HELM than for CTR. Although differences among treatments were observed in carcass fat cover, intramuscular fat did not differ among treatments. Limiting the amount of feed delivery per feeder visit in steers fed high-energy (fat) diets affected eating pattern, reduced total energy consumption and performance, and modified hormones related to intake compared with CTR and HE, but no effect on rib fat distribution and meat quality was observed.

Topics: Animal Feed; Animals; Blood Glucose; Body Composition; Body Weight; Cattle; Cholecystokinin; Diet; Dietary Fats; Energy Metabolism; Feeding Behavior; Food Quality; Glucagon-Like Peptide 1; Insulin; Male; Meat; Random Allocation

Cholecystokinin (CCK) is anorexic, irrespective whether it is applied intraperitoneally (IP) or intracerebroventricularly (ICV) in male Wistar rats. The metabolic effects depend on the route of administration: by the IP route it elicits hypothermia (presumably by type-1 receptors, CCK1R-s), while ICV administration is followed by fever-like hypermetabolism and hyperthermia via activation of CCK2R-s, which latter response seems to be most important in the postprandial (compensatory) hypermetabolism. The efficacy of the IP injected CCK varies with age: it causes strong anorexia in young adult 4 and 6-months old and again in old rats (aged 18-24 months), but the middle-aged (12-month old) ones seem to be resistant to this effect. Such pattern of effects may contribute to the explanation of age-related obesity observed in middle-aged animals as well as to the aging anorexia and loss of body weight in old ones. Diet-induced obesity accelerates the appearance of CCK-resistance as well as the return of high sensitivity to CCK in further aging, while chronic calorie-restriction prevents the development of resistance, as if the speed of the age-related regulatory changes was altered by the nutritional state. The effects of ICV applied CCK also change with age: the characteristic anorexic and hypermetabolic/hyperthermic effects can be observed in young adult rats, but the effects gradually and monotonically decline with age and disappear by the old age of 24 months. These disparate age-related patterns of CCK efficacy upon peripheral or central administration routes may indicate that although both peripheral and central CCKR-s exert anorexic effects, they may have dissimilar roles in the regulation of overall energy balance.

Topics: Aging; Animals; Anorexia; Body Temperature Regulation; Body Weight; Caloric Restriction; Cholecystokinin; Diet, High-Fat; Eating; Energy Metabolism; Injections, Intraperitoneal; Injections, Intraventricular; Male; Nutritional Status; Obesity; Rats; Rats, Wistar

Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL) in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10), the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14) and the control group including healthy adolescents (n = 14). Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p < 0.005) and the control group (p < 0.005). Mean plasma GIP levels in the control group were lower than in the non-HPG group (p < 0.003) and the HPG group (p < 0.01). We conclude that the regulation of HGL secretion by GLP-1 and CCK is altered in patients with gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis.

Topics: Adolescent; Body Mass Index; Body Weight; Case-Control Studies; Cholecystokinin; Fasting; Gastric Inhibitory Polypeptide; Gastritis; Gastrointestinal Tract; Glucagon-Like Peptide 1; Helicobacter Infections; Humans; Hydrogen-Ion Concentration; Lipase; Young Adult

Ghrelin is an orexigenic peptide that stimulates food intake, whereas peptide YY (PYY) and cholecystokinin (CCK) are anorexigenic gut hormones. Patients with polycystic ovary syndrome (PCOS) appear to have alterations in appetite regulation.. We aimed to determine whether fasting or meal-stimulated ghrelin, PYY, CCK, and satiety responses are different between lean PCOS patients and healthy women. We also aimed to assess the potential effect of oral contraceptive use on these hormones and satiety response.. We conducted a prospective observational study in a university practice.. Eighteen lean PCOS patients and 18 healthy control women matched for age and body mass index underwent measurements of circulating ghrelin, PYY, CCK, and satiety index (SI) before and after a standardized mixed meal at 0, 15, 30, 45, 60, 90, 120, and 180 minutes.. For PCOS patients who were treated with ethinyl estradiol 30 μg/drospirenone 3 mg for 3 months, measurements were repeated.. We measured ghrelin, PYY, and CCK levels and SI.. At baseline, fasting ghrelin, PYY, CCK, and SI values in PCOS patients were not different from controls. Meal-stimulated PYY, CCK, and SI were also not different between the groups, whereas PCOS patients had significantly lower meal-stimulated ghrelin levels compared to controls (P = .04). Ghrelin, PYY, CCK, and SI did not show a significant change after treatment with ethinyl estradiol/drospirenone for 3 months.. Basal and stimulated hunger and satiety hormones in lean PCOS patients are not different from lean healthy women, except for a lower meal-stimulated ghrelin response. Short-term use of a low-dose oral contraceptive does not have an effect on appetite regulation of PCOS.

Topics: Adolescent; Adult; Androstenes; Basal Metabolism; Body Weight; Cholecystokinin; Contraceptives, Oral; Eating; Estrogens; Ethinyl Estradiol; Female; Ghrelin; Humans; Mineralocorticoid Receptor Antagonists; Peptide YY; Polycystic Ovary Syndrome; Prospective Studies; Satiety Response; Young Adult

The gastrointestinal hormone cholecystokinin (CCK) plays an important role in regulating meal size and duration by activating CCK1 receptors on vagal afferent neurons (VAN). Leptin enhances CCK signaling in VAN via an early growth response 1 (EGR1) dependent pathway thereby increasing their sensitivity to CCK. In response to a chronic ingestion of a high fat diet, VAN develop leptin resistance and the satiating effects of CCK are reduced. We tested the hypothesis that leptin resistance in VAN is responsible for reducing CCK signaling and satiation.. Lean Zucker rats sensitive to leptin signaling, significantly reduced their food intake following administration of CCK8S (0.22 nmol/kg, i.p.), while obese Zucker rats, insensitive to leptin, did not. CCK signaling in VAN of obese Zucker rats was reduced, preventing CCK-induced up-regulation of Y2 receptor and down-regulation of melanin concentrating hormone 1 receptor (MCH1R) and cannabinoid receptor (CB1). In VAN from diet-induced obese (DIO) Sprague Dawley rats, previously shown to become leptin resistant, we demonstrated that the reduction in EGR1 expression resulted in decreased sensitivity of VAN to CCK and reduced CCK-induced inhibition of food intake. The lowered sensitivity of VAN to CCK in DIO rats resulted in a decrease in Y2 expression and increased CB1 and MCH1R expression. These effects coincided with the onset of hyperphagia in DIO rats.. Leptin signaling in VAN is required for appropriate CCK signaling and satiation. In response to high fat feeding, the onset of leptin resistance reduces the sensitivity of VAN to CCK thus reducing the satiating effects of CCK.

Topics: Animals; Body Weight; Cells, Cultured; Cholecystokinin; Diet, High-Fat; Eating; Leptin; Male; Neurons, Afferent; Obesity; Phenotype; Rats; Rats, Sprague-Dawley; Rats, Zucker; Satiation; Signal Transduction; Vagus Nerve

Feeding behavior and reproduction are coordinately regulated by the brain via neurotransmitters, circulating hormones, and neuropeptides. Reduced feeding allows animals to engage in other behaviors important for fitness, including mating and parental care. Some fishes cease feeding for weeks at a time in order to provide care to their young by brooding them inside the male or female parent's mouth. Maternal mouthbrooding is known to impact circulating hormones and subsequent reproductive cycles, but neither the full effects of food deprivation nor the neural mechanisms are known. Here we ask what effects mouthbrooding has on several physiological processes including gonad and body mass, brain neuropeptide and receptor gene expression, and circulating steroid hormones in a mouthbrooding cichlid species, Astatotilapia burtoni. We ask whether any observed changes can be explained by food deprivation, and show that during mouthbrooding, ovary size and circulating levels of androgens and estrogens match those seen during food deprivation. Levels of gonadotropin-releasing hormone 1 (GnRH1) mRNA in the brain were low in food-deprived females compared to controls and in mouthbrooding females compared to gravid females. Levels of mRNA encoding two peptides involved in regulating feeding, hypocretin and cholecystokinin, were increased in the brains of food-deprived females. Brain mRNA levels of two receptors, GnRH receptor 2 and NPY receptor Y8c, were elevated in mouthbrooding females compared to the fed condition, but NPY receptor Y8b mRNA was differently regulated by mouthbrooding. These results suggest that many, but not all, of the characteristic physiological changes that occur during mouthbrooding are consequences of food deprivation.

Topics: Androgens; Animals; Body Weight; Brain; Cholecystokinin; Cichlids; Estrogens; Female; Food Deprivation; Gonadotropin-Releasing Hormone; Intracellular Signaling Peptides and Proteins; Neuropeptides; Orexins; Organ Size; Ovary; Protein Precursors; Receptors, LHRH; Receptors, Neuropeptide Y; Reproduction; RNA, Messenger

The aim of this paper was to investigate the effect of heat stress on the regulation of appetite-associated genes in laying hens. Forty eight laying hens were randomly divided into two circumstances: high (31 ± 1.5°C; relative humidity, 82.0 ± 2.2%) or normal (20 ± 2°C, control; relative humidity, 60.1 ± 4.5%) ambient environment. Heat stress decreased body weight gain (P < 0.01), feed intake (P < 0.01), laying rate (P < 0.05), average egg mass (P < 0.01), egg production (P < 0.01), shell thickness (P < 0.01), and feed efficiency (P < 0.05). High ambient temperature decreased plasma uric acid (P < 0.05). Heat stress significantly increased mRNA levels of ghrelin and cocaine- and amphetamine-regulated transcript (P < 0.05) and decreased mRNA levels of cholecystokinin (P < 0.05) in the hypothalamus. Heat stress significantly increased (P < 0.05) mRNA levels of ghrelin in the glandular stomach and jejunum but significantly decreased (P < 0.05) mRNA levels of cholecystokinin in the duodenum and jejunum. In conclusion, heat stress plays a unique role in some special neuropeptides (e.g., ghrelin, cocaine- and amphetamine-regulated transcript, and cholecystokinin), which might participate in the regulation of feed intake in laying hens under high ambient temperature.

Topics: Animals; Appetite Regulation; Body Weight; Chickens; Cholecystokinin; Clutch Size; Eating; Egg Shell; Female; Gene Expression Profiling; Gene Expression Regulation; Heat-Shock Response; Hypothalamus; Neuropeptides; Organ Specificity; Oviposition; Peptide Hormones; RNA, Messenger

Protein level in the maternal diet plays a crucial role in fetal programming during pregnancy. Low or high protein level increases the risk of intrauterine growth retardation (IUGR). The aim of this study was to investigate the structural and functional development of the small intestine in piglets from sows fed a control (C, 12.1% protein), a high protein (HP, 30% protein), or a low protein (LP, 6.5% protein) diet during pregnancy. Newborns were classified as IUGR (birth weight ≤1.18 kg) and non-IUGR (birth weight >1.18 kg). The piglets were euthanized on postnatal day (PD)1, PD28 and PD188. The LP diet in non-IUGR neonates resulted in decreased body weight on PD1. The LP and HP diets resulted in both decreased body weight and delayed catch-up growth in the IUGR piglets. The HP and LP-diets increased the length of villi on PD1 in non-IUGRs but not in IUGRs. At birth, the expressions of Ki67 and active caspase 3 in mid-jejunum epithelium of HP and LP non-IUGR neonates were significantly lower as compared to C non-IUGRs whilst in IUGRs the respective expressions were as high as in C non-IUGRs. The postnatal dynamics of brush border enzyme activities and vacuolated enterocytes disappearance showed significant drop in enterocyte maturation in IUGR as compared to non-IUGR neonates. In conclusion, both HP and LP diets led to retarded development of non-IUGR piglets. In IUGR piglets both HP and LP diets resulted in delayed catch-up growth, without adaptive changes in brush border digestive enzymes.

Topics: Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Apoptosis; Birth Weight; Body Weight; Caspase 3; Cholecystokinin; Cytokines; Diet; Dietary Proteins; Female; Fetal Development; Fetal Growth Retardation; Glucagon-Like Peptides; Inflammation; Intestinal Mucosa; Jejunum; Ki-67 Antigen; Male; Mitosis; Pregnancy; Pregnancy Complications; Random Allocation; RNA, Messenger; Sus scrofa

The action of peripherally released leptin at long-form leptin receptors (LepRb) within the brain represents a fundamental axis in the regulation of energy homeostasis and body weight. Efforts to delineate the neuronal mediators of leptin action have recently focused on extrahypothalamic populations and have revealed that leptin action within the nucleus of the solitary tract (NTS) is critical for normal appetite and body weight regulation. To elucidate the neuronal circuits that mediate leptin action within the NTS, we employed multiple transgenic reporter lines to characterize the neurochemical identity of LepRb-expressing NTS neurons. LepRb expression was not detected in energy balance-associated NTS neurons that express cocaine- and amphetamine-regulated transcript, brain-derived neurotrophic factor, neuropeptide Y, nesfatin, catecholamines, γ-aminobutyric acid, prolactin-releasing peptide, or nitric oxide synthase. The population of LepRb-expressing NTS neurons was comprised of subpopulations marked by a proopiomelanocortin-enhanced green fluorescent protein (EGFP) transgene and distinct populations that express proglucagon and/or cholecystokinin. The significance of leptin action on these three populations of NTS neurons was assessed in leptin-deficient Ob/Ob mice, revealing increased NTS proglucagon and cholecystokinin, but not proopiomelanocortin, expression. These data provide new insight into the appetitive brainstem circuits engaged by leptin.

Topics: Animals; Body Weight; Brain-Derived Neurotrophic Factor; Cholecystokinin; Energy Metabolism; gamma-Aminobutyric Acid; Leptin; Mice; Mice, Transgenic; Neurons; Neuropeptide Y; Phosphorylation; Pro-Opiomelanocortin; Proglucagon; Prolactin-Releasing Hormone; Receptors, Leptin; Solitary Nucleus; STAT3 Transcription Factor

Intrauterine growth restriction (IUGR) is associated with a substantially greater incidence of metabolic syndrome in adulthood. Animal studies have shown that IUGR offspring are hyperphagic during the early postnatal period and therefore exhibit obesity. The molecular mechanisms underlying food intake regulation in the gastrointestinal tract have not been clarified in IUGR. In the present study, we utilized a rat model of IUGR by restricting the food intake of the mother (50% of the normal intake, ad libitum; FR group) from day 7 of gestation until delivery. Pups from undernourished mothers were fostered by control mothers. We examined the food intake and assessed the gene expressions of ghrelin, peptide YY (PYY), and cholecystokinin (CCK) in the alimentary tract of male newborns (postnatal day1) and adult offspring (age, 7 months). Compared to the offspring whose mothers received the standard diet ad libitum (CON offspring), FR offspring were hyperphagic from the weaning time until the end of the experiment, and resulted in a heavier final weight. Both newborn and adult FR offspring had higher ghrelin gene expression in the stomach and higher ghrelin plasma levels than did the controls. Although the gastrointestinal gene expressions and plasma levels of the anorexic peptides, PYY and CCK, were elevated in the FR newborns, they decreased in the FR adults. Our findings suggest that the altered gene expressions of orexigenic and anorexigenic gut peptides in the gastrointestinal tract in the maternal undernutrition-induced IUGR offspring provide a potential mechanism to explain hyperphagia and obesity seen in these offspring.

Topics: Adult; Animals; Animals, Newborn; Body Weight; Cholecystokinin; Disease Models, Animal; Eating; Female; Fetal Growth Retardation; Gastrointestinal Tract; Gene Expression; Gene Expression Regulation, Developmental; Ghrelin; Humans; Hyperphagia; Male; Peptide YY; Rats; Rats, Sprague-Dawley; Up-Regulation

Obese patients with type II diabetes who undergo bariatric surgery revert to normal blood glucose and insulin levels, and develop a dramatic increase in insulin sensitivity. However, the mechanisms involved are unknown. This study characterized pancreatic islet and duodenojejunal enteroendocrine cells in normal mice and those with diabetes induced by a high-fat diet (HFD) following duodenojejunal bypass (DJB).. C57BL/6J mice, fed for 8 weeks either a normal diet (n = 10) or a HFD (n = 10) resulting in a hyperglycaemic state, underwent DJB (connection of the distal end of the jejunum to the distal stomach and direction of biliopancreatic secretions to the distal jejunum). Metabolic and immunohistological analyses were carried out on the pancreas and gastrointestinal tract.. A significant decrease in fasting blood glucose was observed in normal-DJB and HFD-DJB mice 1 week after the operation, with improved glucose tolerance at 4 weeks. There were no changes in pancreatic β-cell mass, but an increase in the ratio of α-cell to β-cell mass was observed in the DJB groups. Furthermore, the number of cells expressing Pdx-1, glucagon-like peptide 1, pancreatic polypeptide and synaptophysin was increased in the bypassed duodenum and/or gastrojejunum of the DJB groups.. Both normal and obese diabetic mice that underwent DJB displayed improved glucose tolerance and a reduction in fasting blood glucose, which mimicked findings in obese diabetic patients following bariatric surgery. The present data suggest that an increase in specific enteroendocrine cell populations may play a critical role in normalizing glucose homeostasis.

Topics: Anastomosis, Surgical; Animals; Blood Glucose; Body Weight; Cholecystokinin; Diabetes Mellitus, Type 2; Diet; Dietary Fats; Duodenum; Eating; Fluorescent Antibody Technique; Glucagon-Like Peptide 1; Homeodomain Proteins; Homeostasis; Islets of Langerhans; Jejunum; Mice; Mice, Inbred C57BL; Mice, Obese; Trans-Activators

Gastrointestinal vagal afferents transmit satiety signals to the brain via both chemical and mechanical mechanisms. There is indirect evidence that these signals may be attenuated in obesity. We hypothesized that responses to satiety mediators and distension of the gut would be attenuated after induction of diet induced obesity. Obesity was induced by feeding a high fat diet (60% kcal from fat). Low fat fed mice (10% kcal from fat) served as a control. High fat fed mice were obese, with increased visceral fat, but were not hyperglycaemic. Recordings from jejunal afferents demonstrated attenuated responses to the satiety mediators cholecystokinin (CCK, 100 nm) and 5-hydroxytryptamine (5-HT, 10 μm), as was the response to low intensity jejunal distension, while responses to higher distension pressures were preserved. We performed whole cell patch clamp recordings on nodose ganglion neurons, both unlabelled, and those labelled by fast blue injection into the wall of the jejunum. The cell membrane of both labelled and unlabelled nodose ganglion neurons was less excitable in HFF mice, with an elevated rheobase and decreased number of action potentials at twice rheobase. Input resistance of HFF neurons was also significantly decreased. Calcium imaging experiments revealed reduced proportion of nodose ganglion neurons responding to CCK and 5-HT in obese mice. These results demonstrate a marked reduction in afferent sensitivity to satiety related stimuli after a chronic high fat diet. A major mechanism underlying this change is reduced excitability of the neuronal cell membrane. This may explain the development of hyperphagia when a high fat diet is consumed. Improving sensitivity of gastrointestinal afferent nerves may prove useful to limit food intake in obesity.

Topics: Action Potentials; Afferent Pathways; Animals; Blood Glucose; Body Weight; Calcium Signaling; Cholecystokinin; Dietary Fats; Electric Impedance; Intestines; Intra-Abdominal Fat; Jejunum; Male; Mechanotransduction, Cellular; Membrane Potentials; Mice; Mice, Inbred C57BL; Neurons; Nodose Ganglion; Obesity; Patch-Clamp Techniques; Satiety Response; Serotonin; Vagus Nerve

One of the possible mechanisms by which the weight-reducing surgical procedure ileal interposition (II) works is by increasing circulating levels of lower gut peptides that reduce food intake, such as glucagon like peptide-1 and peptide YY. However, since this surgery involves both lower and upper gut segments, we tested the hypothesis that II alters the satiety responses evoked by the classic upper gut peptide cholecystokinin (CCK). To test this hypothesis, we determined meal size (MS), intermeal interval (IMI) and satiety ratio (SR) evoked by CCK-8 and -33 (0, 1, 3, 5nmol/kg, i.p.) in two groups of rats, II and sham-operated. CCK-8 and -33 reduced MS more in the sham group than in the II group; CCK-33 prolonged IMI in the sham group and increased SR in both groups. Reduction of cumulative food intake by CCK-8 in II rats was blocked by devazepide, a CCK(1) receptor antagonist. In addition, as previously reported, we found that II resulted in a slight reduction in body weight compared to sham-operated rats. Based on these observations, we conclude that ileal interposition attenuates the satiety responses of CCK. Therefore, it is unlikely that this peptide plays a significant role in reduction of body weight by this surgery.

Topics: Animals; Body Weight; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Eating; Feeding Behavior; Ileum; Jejunoileal Bypass; Jejunum; Male; Peptide Fragments; Rats; Rats, Wistar; Receptors, Cholecystokinin; Satiety Response

Deficits in satiation signals are strongly suspected of accompanying obesity and contributing to its pathogenesis in both humans and rats. One such satiation signal is cholecystokinin (CCK), whose effects on food intake are diminished in animals adapted to a high fat diet. In this study, we tested the hypothesis that diet-induced obese prone (OP) rats exhibit altered feeding and vagal responses to systemic (IP) administration of CCK-8 compared to diet-induced obese resistant (OR) rats. We found that CCK (4.0 microg/kg) suppressed food intake significantly more in OP than OR rats. To determine whether enhanced suppression of feeding is accompanied by altered vagal sensory responsiveness, we examined dorsal hindbrain expression of Fos-like immunoreactivity (Fos-Li) following IP CCK injection in OP and OR rats. After 4.0 microg/kg CCK, there were significantly more Fos-positive nuclei in the NTS of OP compared to OR rats. Treatment with 8.0 microg/kg CCK resulted in no significant difference in food intake or in Fos-Li between OP and OR rats. Also, we found that OP rats were hyperphagic on a regular chow diet and gained more weight compared to OR rats. Finally OP rats had decreased relative fat pad mass compared to OR rats. Collectively, these results show that OP rats exhibit a different behavioral and vagal neuronal responses to CCK than OR rats.

Topics: Adiposity; Analysis of Variance; Animals; Body Weight; Cell Count; Cholecystokinin; Diet; Eating; Feeding Behavior; Hyperphagia; Immunohistochemistry; Neurons; Obesity; Proto-Oncogene Proteins c-fos; Random Allocation; Rats; Rats, Sprague-Dawley; Rhombencephalon; Satiety Response; Time Factors; Vagus Nerve

The objectives of the present study were 1) to evaluate the effects of supplemental fat and ME intake on plasma concentrations of glucagon-like peptide-1 (GLP-1), cholecystokinin (CCK), glucose-dependent insulinotropic polypeptide, ghrelin, and oxyntomodulin; and 2) to determine the association of these peptides with DMI and the hypothalamic concentration of mRNA for the following neuropeptides: neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin (POMC). In a completely randomized block design with a 2 x 2 factorial arrangement of treatments, 32 pens with 2 wethers each were restricted-fed (2.45 Mcal/lamb per day) or offered diets ad libitum (n = 16) with or without 6% supplemental fat (n = 16) for a period of 30 d. Dry matter intake was measured daily. On d 8, 15, 22, and 29, BW was measured before feeding, and 6 h after feeding, blood samples were collected for plasma measurement of insulin, GLP-1, CCK, ghrelin, glucose-dependent insulinotropic polypeptide, oxyntomodulin, glucose, and NEFA concentrations. On d 29, blood was collected 30 min before feeding for the same hormone and metabolite analyses. At the end of the experiment, wethers were slaughtered and the hypothalami were collected to measure concentrations of NPY, AgRP, and POMC mRNA. Offering feed ad libitum (resulting in greater ME intake) increased plasma insulin and NEFA concentrations (P = 0.02 and 0.02, respectively) and decreased hypothalamic mRNA expression of NPY and AgRP (P = 0.07 and 0.02, respectively) compared with the restricted-fed wethers. There was a trend for the addition of dietary fat to decrease DMI (P = 0.12). Addition of dietary fat decreased insulin and glucose concentrations (P < 0.05 and 0.01, respectively) and tended to increase hypothalamic mRNA concentrations for NPY and AgRP (P = 0.07 and 0.11, respectively). Plasma GLP-1 and CCK concentrations increased in wethers offered feed ad libitum compared with restricted-fed wethers, but the response was greater when wethers were offered feed ad libitum and had supplemental fat in the diet (fat x intake interaction, P = 0.04). The prefeeding plasma ghrelin concentration was greater in restricted-fed wethers compared with those offered feed ad libitum, but the concentrations were similar 6 h after feeding (intake x time interaction, P < 0.01). Supplemental dietary fat did not affect (P = 0.22) plasma ghrelin concentration. We conclude that insulin, ghrelin, CCK, and GLP-1 may regulate DMI in sheep by

Topics: Animals; Body Weight; Cholecystokinin; Dietary Fats; Eating; Fasting; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Hypothalamus; Male; Oxyntomodulin; Peptide Fragments; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sheep

Cholecystokinin (CCK) acutely synergizes with amylin to suppress food intake in lean mice. To extend on these findings, the present studies sought to identify neural correlates for the interaction of amylin and CCK, as well as further understand the therapeutic potential of CCK-based combinations in obesity. First, c-Fos activation was assessed in various brain nuclei after a single intraperitoneal injection of amylin (5microg/kg) and/or CCK (5microg/kg). Amylin and CCK additively increased c-Fos within the area postrema (AP), predominantly in noradrenergic (e.g., dopamine-beta-hydroxylase-containing) cells. Next, amylin (100 or 300microg/kg/d) and/or CCK (100 or 300microg/kg/d) were subcutaneously infused for 7days in diet-induced obese (DIO) rats. Amylin treatment of DIO rats for 7days induced significant body weight loss. CCK, while ineffective alone, significantly enhanced body weight loss when co-administered with the higher dose of amylin. Finally, the addition of CCK (300microg/kg/d) to leptin (125microg/kg/d), and to the combination of amylin (50microg/kg/d) and leptin (125microg/kg/d), was also explored in DIO rats via sustained subcutaneous infusion for 14days. Infusion of amylin/leptin/CCK for 14days exerted significantly greater body weight loss, inhibition of food intake, and reduction in adiposity compared to amylin/leptin treatment alone in DIO rats. However, co-infusion of CCK and leptin was an ineffective weight loss regimen in this model. Whereas CCK agonism alone is ineffective at eliciting or maintaining weight loss, it durably augmented the food intake and body weight-lowering effects of amylin and amylin/leptin in a relevant disease model, and when combined with amylin, cooperatively activated neurons within the caudal brainstem.

Topics: Amyloid; Analysis of Variance; Animals; Appetite Depressants; Area Postrema; Body Weight; Cholecystokinin; Disease Models, Animal; Dopamine beta-Hydroxylase; Dose-Response Relationship, Drug; Drug Therapy, Combination; Eating; Islet Amyloid Polypeptide; Leptin; Male; Neurons; Obesity; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Weight Loss

Adult rats chronically fed a high-fat (HF) diet maintain reduced sensitivity to cholecystokinin (CCK). We hypothesized that, similar to adult rats, pups fed a HF diet would also exhibit reduced sensitivity to CCK. To test this, male pups fed low-fat (LF) and HF isoenergetic (16.2 kJ/g) diets were administered CCK intraperitoneally (0.125-1 microg/kg) 1 wk following dietary adaptation. After receiving 0.5 microg/kg CCK, pups fed the HF diet suppressed food intake less (8.9 +/- 5.0%) than pups fed the LF diet (28.9 +/- 4.7%; P < 0.05) relative to intakes after saline administration. We then assessed the development and extinction of changes in CCK sensitivity by switching the diets between the groups. The HF-fed group, when switched to the LF diet, regained sensitivity by wk 4 and suppressed food intake following administration of 0.25 microg/kg CCK (33.1 +/- 5.7%; P < 0.05). The LF-fed group, when switched to the HF diet, lost sensitivity by wk 2 and did not suppress food intake after administrations of CCK compared with saline. Finally, we examined if HF-fed rats have an increased sensitivity to corn oil during brief access tests using a multibottle gustometer. At oil concentrations of 25, 75, and 100%, rats fed the HF diet sampled more oil than LF-fed rats (P < 0.05). These findings demonstrate that male rat pups fed a HF diet exhibit reduced sensitivity to CCK, the development of this reduced sensitivity is quicker than its extinction, and rats consuming a HF diet have increased oral sensitivity to oils.

Topics: Animals; Body Weight; Cholecystokinin; Dietary Fats; Eating; Energy Intake; Male; Rats; Rats, Sprague-Dawley; Satiety Response

A previous study demonstrated that ginseng crude saponins prevent obesity induced by a high-fat diet in rats. Ginseng crude saponins are known to contain a variety of bioactive saponins. The present study investigated and compared the antiobesity activity of protopanaxadiol (PD) and protopanaxatriol (PT) type saponins, major active compounds isolated from crude saponins. Male 4-week-old Sprague-Dawley rats were fed with normal diet (N) or high-fat diet (HF). After 5 weeks, the HF diet group was subdivided into the control HF diet, HF diet-PD and HF diet-PT group (50 mg/kg/day, 3 weeks, i.p.). Treatment with PD and PT in the HF diet group reduced the body weight, total food intake, fat contents, serum total cholesterol and leptin to levels equal to or below the N diet group. The hypothalamic expression of orexigenic neuropeptide Y was significantly decreased with PD or PT treatment, whereas that of anorexigenic cholecystokinin was increased, compared with the control HF diet group. In addition, PD type saponins had more potent antiobesity properties than PT saponins, indicating that PD-type saponins are the major components contributing to the antiobesity activities of ginseng crude saponins. The results suggest that the antiobesity activity of PD and PT type saponins may result from inhibiting energy gain, normalizing hypothalamic neuropeptides and serum biochemicals related to the control of obesity.

Topics: Animals; Anti-Obesity Agents; Body Weight; Cholecystokinin; Cholesterol; Eating; Hypothalamus; Leptin; Male; Neuropeptide Y; Obesity; Panax; Rats; Rats, Sprague-Dawley; Sapogenins; Triglycerides

Resistant starch (RS) is fermentable dietary fiber. Inclusion of RS in the diet causes decreased body fat accumulation and altered gut hormone profile. This study investigates the effect of feeding RS on the neuropeptide messenger RNA (mRNA) expressions in the arcuate nucleus (ARC) of the hypothalamus and whether vagal afferent nerves are involved. The rats were injected intraperitoneally with capsaicin to destroy unmyelinated small vagal afferent nerve fibers. The cholecystokinin (CCK) food suppression test was performed to validate the effectiveness of the capsaicin treatment. Then, capsaicin-treated rats and vehicle-treated rats were subdivided into a control diet or a RS diet group, and fed the corresponding diet for 65 days. At the end of study, body fat, food intake, plasma peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), and hypothalamic pro-opiomelanocortin (POMC), neuropeptide Y (NPY), agouti-related peptide (AgRP) gene expressions were measured. RS-fed rats had decreased body fat, increased POMC expression in the hypothalamic ARC, and elevated plasma PYY and GLP-1 in both the capsaicin and vehicle-treated rats. Hypothalamic NPY and AgRP gene expressions were not changed by RS or capsaicin. Therefore, destruction of the capsaicin-sensitive afferent nerves did not alter the response to RS in rats. These findings suggest that dietary RS might reduce body fat through increasing the hypothalamic POMC expression and vagal afferent nerves are not involved in this process. This is the first study to show that dietary RS can alter hypothalamic POMC expression.

Topics: Agouti-Related Protein; Animal Feed; Animals; Body Weight; Capsaicin; Cholecystokinin; Dietary Fiber; Energy Intake; Gene Expression Regulation; Glucagon-Like Peptide 1; Hypothalamus; Male; Peptide YY; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley

Glucocorticoids have major effects on food intake, demonstrated by the decrease of food intake following adrenalectomy. Satiety signals are relayed to the nucleus of the solitary tract (NTS), which has reciprocal projections with the arcuate nucleus (ARC) and paraventricular nucleus (PVN) of the hypothalamus. We evaluated the effects of glucocorticoids on the activation of hypothalamic and NTS neurons induced by food intake in rats subjected to adrenalectomy (ADX) or sham surgery 7 days before the experiments. One-half of ADX animals received corticosterone (ADX+B) in the drinking water (B: 25 mg/l). Fos/tyrosine hydroxylase (TH), Fos/corticotrophin-releasing factor (CRF) and Fos immunoreactivity were assessed in the NTS, PVN, and ARC, respectively. Food intake and body weight were reduced in the ADX group compared with sham and ADX+B groups. Fos and Fos/TH in the NTS, Fos, and Fos/CRF immunoreactive neurons in the PVN and Fos in the ARC were increased after refeeding, with higher number in the ADX group, compared with sham and ADX+B groups. CCK administration showed no hypophagic effect on ADX group despite a similar increase of Fos/TH immunoreactive neurons in the NTS compared with sham and ADX+B groups, suggesting that CCK alone cannot further increase the anorexigenic effect induced by glucocorticoid deficiency. The present data indicate that glucocorticoid withdrawal reduced food intake, which was associated with higher activation of ARC, CRF neurons of the PVN, and catecholaminergic neurons of the NTS. In the absence of glucocorticoids, satiety signals elicited during a meal lead to an augmented activation of brain stem and hypothalamic pathways.

Topics: Adrenalectomy; Animals; Arcuate Nucleus of Hypothalamus; Behavior, Animal; Body Weight; Catecholamines; Cholecystokinin; Corticosterone; Corticotropin-Releasing Hormone; Disease Models, Animal; Drinking; Eating; Fasting; Feeding and Eating Disorders; Glucocorticoids; Hypothalamus; Male; Neural Pathways; Neurons; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; Satiety Response; Solitary Nucleus; Tyrosine 3-Monooxygenase

Cholecystokinin (CCK) is a short acting satiating peptide hormone produced in the proximal small intestine. Daily CCK injection in rats initially inhibits food intake, but after several days, food intake is no longer affected, suggesting development of tolerance. Previously, we covalently coupled CCK to a 10kDa polyethylene glycol (mPEG-OH) and showed that this conjugate, PEG-CCK(9), produced a significantly longer anorectic effect than unmodified CCK(9). The present study examined whether tolerance to the anorectic effect develops during long-term administration of PEG-CCK(9). For 14 consecutive days, male Wistar rats (n=12) received a daily i.p injection of 8microgkg(-1) of PEG-CCK(9) and a control group received a daily control injection of mPEG-OH. Body weight and food intake were monitored daily during the experiment. Effects on the pancreas were investigated. On each day, injection of PEG-CCK(9) induced an anorectic effect lasting 3-6h, but failed to significantly reduce daily total food intake compared to controls. The body weight gain of the PEG-CCK(9)-treated animals was not different from controls. The PEG-CCK(9)-treated group had a significantly higher pancreas weight, mainly due to hyperplasia. In conclusion, PEG-CCK(9) continued to have a daily suppressive effect on food intake when administered for 14 consecutive days, showing there was no development of tolerance.

Topics: Animals; Body Weight; Cholecystokinin; Drug Tolerance; Feeding Behavior; Injections, Intraperitoneal; Kidney Function Tests; Liver Function Tests; Male; Pancreas; Polyethylene Glycols; Rats; Rats, Wistar

A large body of evidence has demonstrated that one mechanism by which cholecystokinin (CCK) inhibits food intake through activation of CCK1 receptors (CCK1R) on vagal afferent neurons that innervate the gastrointestinal tract and project to the hindbrain. OLETF rats, which carry a spontaneous null mutation of the CCK1R, are hyperphagic, obese, and predisposed to type 2 diabetes. Recently, by introgressing the OLETF-derived, CCK1R-null gene onto a Fischer 344 genetic background, we have been able to generate a CCK1R-deficient, congenic rat strain, F344.Cck1r(-/-), that in contrast to OLETF rats, possesses a lean and normoglycemic phenotype. In the present study, the behavioral and neurobiological phenotype of this rat strain was characterized more fully. As expected, intraperitoneal injections of CCK-8 inhibited intake of chow and Ensure Plus and induced Fos responses in the area postrema and the gelatinosus, commissural and medial subdivisions of the nucleus tractus solitarius of wild-type F344.Cck1r(+/+) rats, whereas CCK-8 was without effect on food intake or Fos induction in the F344.Cck1r(-/-) rats. F344.Cck1r(-/-) and F344.Cck1r(+/+) rats did not differ in body weight and showed comparable weight gain when maintained on Ensure Plus for 2 weeks. Also, no difference was found in 24-h food intake, and dark-phase meal frequency or meal size between F344.Cck1r(+/+) and F344.Cck1r(-/-) rats. As expected, blockade of endogenous CCK action at CCK1R increased food intake and blocked the effects of peripheral CCK-8 in wild-type F344.Cck1r(+/+) rats. These results confirm that in rats with a F344 background, CCK-1R mediates CCK-8-induced inhibition of food intake and Fos activation in the hindbrain and demonstrate that selective genetic ablation of CCK1R is not associated with altered meal patterns, hyperphagia, or excessive weight gain on a palatable diet.

Topics: Animals; Body Weight; Cholecystokinin; Eating; Feeding Behavior; Genotype; Immunohistochemistry; Injections, Intraperitoneal; Male; Peptide Fragments; Polymerase Chain Reaction; Proto-Oncogene Proteins c-fos; Rats; Rats, Inbred F344; Rats, Transgenic; Receptor, Cholecystokinin A

Previous studies have suggested that neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) serves as an important signaling peptide in the regulation of energy balance. To elucidate such actions, we used the adenoassociated virus (AAV) system to alter Npy gene expression in the DMH and examined the effects of these alterations on food intake and energy balance as well as explored its downstream signaling pathway. We found that AAV-mediated overexpression of NPY in the DMH of lean rats increased food intake and body weight, and exacerbated high-fat diet-induced obesity. Knockdown of NPY expression in the DMH via AAV-mediated RNA interference ameliorated the hyperphagia, obesity, and diabetes of Otsuka Long-Evans Tokushima Fatty (OLETF) rats. NPY knockdown in the DMH produced a nocturnal and meal size-specific feeding effect. Moreover, we found that knockdown of DMH NPY expression in intact rats reduced NPY content in the nucleus of the solitary tract (NTS) and the dorsal motor nucleus of the vagus and affected within-meal satiation. DMH NPY knockdown increased the feeding inhibitory and NTS c-Fos responses to peripheral administration of cholecystokinin. Together, these results indicate that DMH NPY plays an important role in modulating food intake and energy balance and its dysregulation causes disordered energy balance leading to obesity.

Topics: Analysis of Variance; Animals; Body Weight; Cell Line, Transformed; Cholecystokinin; Dependovirus; Dorsomedial Hypothalamic Nucleus; Eating; Energy Metabolism; Feeding Behavior; Gene Expression Regulation; Glucose Tolerance Test; Green Fluorescent Proteins; Humans; Male; Neuropeptide Y; Proto-Oncogene Proteins c-fos; Rats; Rats, Inbred OLETF; Rats, Sprague-Dawley; RNA Interference; Solitary Nucleus; Time Factors

Thylakoids are membranes isolated from plant chloroplasts which have previously been shown to inhibit pancreatic lipase/colipase catalysed hydrolysis of fat in vitro and induce short-term satiety in vivo. The purpose of the present study was to examine if dietary supplementation of thylakoids could affect food intake and body weight during long-term feeding in mice. Female apolipoprotein E-deficient mice were fed a high-fat diet containing 41% of fat by energy with and without thylakoids for 100 days. Mice fed the thylakoid-enriched diet had suppressed food intake, body weight gain and body fat compared with the high-fat fed control mice. Reduced serum glucose, serum triglyceride and serum free fatty acid levels were found in the thylakoid-treated animals. The satiety hormone cholecystokinin was elevated, suggesting this hormone mediates satiety. Leptin levels were reduced, reflecting a decreased fat mass. There was no sign of desensitization in the animals treated with thylakoids. The results suggest that thylakoids are useful to suppress appetite and body weight gain when supplemented to a high-fat food during long-term feeding.

Topics: Adipose Tissue; Animals; Appetite; Appetite Depressants; Blood Glucose; Body Weight; Chlorophyll; Cholecystokinin; Dietary Fats; Eating; Fatty Acids; Female; Leptin; Lipase; Mice; Mice, Knockout; Satiety Response; Spinacia oleracea; Thylakoids; Triglycerides

Extracts of kidney beans ( Phaseolus vulgaris ) are known to reduce food intake and glycemia in rodents and humans. This study evaluated the effect of a novel extract of P. vulgaris on food (regular food pellets, starch-enriched diet, and chocolate-flavored beverage) intake, body weight, and glycemia in rats. The effect of the combination of the colecistokinin (CCK) receptor antagonist, lorglumide, and P. vulgaris dry extract on food intake was also investigated. Administration of doses of P. vulgaris dry extract devoid of any behavioral toxicity dose-dependently decreased food intake (irrespective of the diet), body weight gain, and glycemia. Pretreatment with lorglumide blocked the reducing effect of P. vulgaris dry extract on food intake. The capacity of this P. vulgaris dry extract to reduce food intake, body weight, and glycemia in rats may be due to (a) inhibition of alpha-amylase, (b) stimulation of CCK release from the intestinal brush border cells, and/or (c) interference with the central mechanism(s) regulating appetite, food intake, and food palatability.

Topics: alpha-Amylases; Animals; Blood Glucose; Body Weight; Cholecystokinin; Drug Interactions; Eating; Energy Intake; Intestines; Male; Microvilli; Phaseolus; Plant Extracts; Proglumide; Rats; Rats, Wistar; Receptors, Cholecystokinin

Cholecystokinin (CCK) is one of the richest neuropeptides in the mammalian brain, which is mainly distributed in the cerebral cortex, hippocampus, thalamus and caudate-putamen. CCK is implicated in a variety of behavioral functions such as food intake, learning, memory, anxiety, pain and neuroprotection. The current research results for CCK are obtained mainly through injection of CCK peptide into the body. The key issues of whether CCK can regulate diet by a central pathway and whether there are long-term regulation effects on diet are still unresolved. In this study, the effects of CCK on food intake in transgenic mice were investigated.. Transgenic mice were created by microinjection of the PDGF-CCK construct into male pronucleus of the zygotes. The genomic phonetype of transgenic mice were identified by PCR. The expression of PDGF-CCK was analyzed by Western blotting. Body weight, plasma glucose, cholesterol and triglycerides were assayed and analyzed.. Two PDGF-CCK transgenic independent lines were established and exhibited a high-levels brain-specific transgene expression compared with that of nontransgenic littermate controls. The food intake of male CCK transgenic mice was decreased by 5% - 10% with the same levels of water consumed compared with wild type mice. The food intake in female mice was not obviously changed. In the transgenic mice the bodyweight was lower and plasma glucose was higher compared with the nontransgenic littermate controls.. The high expression of the CCK gene in the brain can decrease body weight and increase plasma glucose. The differences in food intake between the males and females require further study.

Topics: Animals; Blood Glucose; Blotting, Western; Body Weight; Brain; Cholecystokinin; Cholesterol; Eating; Female; Lipase; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic

Early life experience impacts emotional development in the infant. In rat pups, repeated, brief (i.e., 15 min) maternal separation (MS15) during the first 1-2 postnatal weeks has been shown to increase active maternal care and to reduce later anxiety-like behavior in the offspring. We hypothesized that the anxiolytic effect of MS15 is partly due to increased intestinal release of cholecystokinin (CCK) in rat pups as a result of increased maternal contact. We predicted that rats with a history of MS15 would display less anxiety in the elevated plus maze (EPMZ) and novelty-suppressed feeding (NSF) tests, as compared with nonseparated (NS) controls, and that the anxiolytic effect of MS15 would be attenuated in rats in which daily MS15 was accompanied by systemic administration of a CCK-1 receptor antagonist (i.e., devazepide). Treatment groups included NS control litters, litters exposed to MS15 from postnatal days (P)1-10, inclusive, and litters exposed to MS15 with concurrent subcutaneous injection of devazepide or vehicle. Litters were undisturbed after P10 and were weaned on P21. Subsets of adolescent males from each litter were tested in the EPMZ on P40-41, while others were tested for NSF on P50-52. As predicted, rats with a developmental history of MS15 displayed reduced anxiety-like behavior in the EPMZ and NSF tests. The anxiolytic effect of MS15 was preserved in vehicle-treated rats, but was reversed in devazepide-treated rats. These results support the view that endogenous CCK-1 receptor signaling in infants is a potential pathway through which maternal-pup interactions regulate the development and functional organization of emotional circuits that control anxiety-like behavior in the offspring.

Topics: Age Factors; Analysis of Variance; Animals; Animals, Newborn; Anxiety; Behavior, Animal; Body Weight; Cholecystokinin; Critical Period, Psychological; Devazepide; Exploratory Behavior; Feeding Behavior; Female; Hormone Antagonists; Male; Maternal Behavior; Maternal Deprivation; Rats; Receptors, Cholecystokinin

Palatable food disrupts normal appetite regulation, which may contribute to the etiology of obesity. Neuropeptide Y (NPY) and cholecystokinin play critical roles in the regulation of food intake and energy homeostasis, while adiponectin and carnitine palmitoyltransferase (CPT) are important for insulin sensitivity and fatty acid oxidation. This study examined the impact of short- and long-term consumption of palatable high-fat diet (HFD) on these critical metabolic regulators.. Male C57BL/6 mice were exposed to laboratory chow (12% fat), or cafeteria-style palatable HFD (32% fat) for 2 or 10 weeks. Body weight and food intake were monitored throughout. Plasma leptin, hypothalamic NPY and cholecystokinin, and mRNA expression of leptin, adiponectin, their receptors and CPT-1, in fat and muscles were measured.. Caloric intake of the palatable HFD group was 2-3 times greater than control, resulting in a 37% higher body weight. Fat mass was already increased at 2 weeks; plasma leptin concentrations were 2.4 and 9 times higher than control at 2 and 10 weeks, respectively. Plasma adiponectin was increased at 10 weeks. Muscle adiponectin receptor 1 was increased at 2 weeks, while CPT-1 mRNA was markedly upregulated by HFD at both time points. Hypothalamic NPY and cholecystokinin content were significantly decreased at 10 weeks.. Palatable HFD induced hyperphagia, fat accumulation, increased adiponectin, leptin and muscle fatty acid oxidation, and reduced hypothalamic NPY and cholecystokinin. Our data suggest that the adaptive changes in hypothalamic NPY and muscle fatty acid oxidation are insufficient to reverse the progress of obesity and metabolic consequences induced by a palatable HFD.

Topics: Adiponectin; Animals; Body Weight; Cholecystokinin; Dietary Fats; Eating; Energy Metabolism; Hyperphagia; Leptin; Male; Mice; Mice, Inbred C57BL; Neuropeptide Y; Obesity; Receptors, Adiponectin; RNA, Messenger

Mice with a targeted disruption of bombesin receptor subtype-3 (BRS-3 KO) develop hyperphagia, obesity, hypertension, and impaired glucose metabolism. However, the factors contributing to their phenotype have not been clearly established. To determine whether their obesity is a result of increased food intake or a defect in energy regulation, we matched the caloric intake of BRS-3 KO mice to wild-type (WT) ad libitum (ad lib)-fed controls over 21 wk. Although BRS-3 KO ad lib-fed mice were 29% heavier, the body weights of BRS-3 KO pair-fed mice did not differ from WT ad lib-fed mice. Pair-feeding BRS-3 KO mice normalized plasma insulin but failed to completely reverse increased adiposity and leptin levels. Hyperphagia in ad lib-fed KO mice was due to an increase in meal size without a compensatory decrease in meal frequency resulting in an increase in total daily food intake. An examination of neuropeptide Y, proopiomelanocortin, and agouti-related peptide gene expression in the arcuate nucleus revealed that BRS-3 KO mice have some deficits in their response to energy regulatory signals. An evaluation of the satiety effects of cholecystokinin, bombesin, and gastrin-releasing peptide found no differences in feeding suppression by these peptides. We conclude that hyperphagia is a major factor leading to increased body weight and hyperinsulinemia in BRS-3 KO mice. However, our finding that pair-feeding did not completely normalize fat distribution and plasma leptin levels suggests there is also a metabolic dysregulation that may contribute to, or sustain, their obese phenotype.

Topics: Adiposity; Animals; Body Weight; Bombesin; Cholecystokinin; Eating; Energy Metabolism; Gastrin-Releasing Peptide; Glucose; Hyperinsulinism; Hyperphagia; Hypothalamus; Insulin; Leptin; Male; Mice; Mice, Knockout; Obesity; Receptors, Bombesin; Satiation; Weight Gain

17beta-estradiol (E2), acting via estrogen receptor (ER)-alpha, inhibits feeding in animals. One mechanism apparently involves an increase in the satiating potency of cholecystokinin (CCK) released from the small intestine by ingested food. For example, the satiating potency of intraduodenal lipid infusions is increased by E2 in ovariectomized rats; this increased satiation is dependent on CCK, and it is accompanied by increases in the numbers of ERalpha-positive cells that express c-Fos in a subregion of the caudal nucleus tractus solitarius (cNTS) that receives abdominal vagal afferent projections. To test whether direct administration of E2 to this area of the hindbrain is sufficient to inhibit food intake, we first implanted 0.2 microg estradiol benzoate (EB) in cholesterol or cholesterol alone either sc or onto the surface of the hindbrain over the cNTS. Food intake was significantly reduced after hindbrain EB implants but not after sc EB implants. Next we verified that equimolar hindbrain implants of E2 and EB had similar feeding-inhibitory effects and determined that only small amounts of E2 reached brain areas outside the dorsal caudal hindbrain after hindbrain implants of (3)H-labeled E2. Neither plasma estradiol concentration nor plasma inflammatory cytokine concentration was increased by either hindbrain or sc EB implants. Finally, hindbrain EB implants, but not sc implants, increased c-Fos in ERalpha-positive cells in the cNTS after ip injection of 4 microg/kg CCK-8. We conclude that E2, acting via ERalpha in cNTS neurons, including neurons stimulated by ip CCK, is sufficient to inhibit feeding.

Topics: Animals; Body Weight; Cholecystokinin; Cytokines; Eating; Estradiol; Estrogen Receptor alpha; Female; Ovariectomy; Proto-Oncogene Proteins c-fos; Rats; Rats, Long-Evans; Rhombencephalon; Solitary Nucleus

CCK acts peripherally as a satiating peptide released during meals in response to lipid feeding and centrally functions in the modulation of feeding, exploratory, and memory activities. The present study determined metabolic parameters, food intake, anxiety-like behaviors, and cognitive function in mice lacking the CCK gene. We studied intestinal fat absorption, body composition, and food intake of CCK knockout (CCK-KO) mice by using the noninvasive measurement of intestinal fat absorption along with quantitative magnetic resonance (QMR) imaging and the DietMax system, respectively. Additionally, exploratory and memory capacities were assessed by monitoring running wheel activity and conducting elevated plus-maze and Morris water-maze tests with these mice. Compared with wild-type (WT) littermate controls, CCK-KO mice had normal food intake, fat absorption, body weight, and body mass. CCK-KO mice ate more food than control animals during the light period and less food during the dark period. Energy expenditure was unchanged between the genotypes; however, CCK-KO mice displayed greater fatty acid oxidation. CCK-KO mice were as active as WT animals in the running wheel test. CCK-KO mice spent more time in the closed arms of an elevated plus-maze, indicative of increased anxiety. Additionally, CCK-KO mice exhibited attenuated performance in a passive avoidance task and impaired spatial memory in the Morris water maze test. We conclude that CCK is involved in metabolic rate and is important for memory and exploration. CCK is intimately involved in multiple processes related to cognitive function and food intake regulation.

Topics: Animals; Anxiety; Avoidance Learning; Body Composition; Body Weight; Cholecystokinin; Cognition; Dietary Fats; Eating; Energy Metabolism; Intestinal Absorption; Male; Maze Learning; Mice; Mice, Inbred C57BL; Mice, Knockout; Motor Activity

Kratom (Mitragyna speciosa Korth.) is an indigenous plant of Thailand used traditionally in folk medicine although it is claimed to cause addiction. It is used to treat diarrhea, however, there is no scientific evidence to support the use. The aim of this study is to investigate the effect of methanolic extract of kratom leaves on the rat gastrointestinal tract. Kratom extract at 50, 100, 200 and 400 mg/kg (p.o.) caused a dose dependent protection against castor oil-induced diarrhea in rats and also inhibited intestinal transit. The antidiarrheal effect was not antagonized by naloxzone. The inhibition of intestinal transit by kratom extract was significantly different from the control when treated with a single dose for 1 day. For longer-term treatments of 15 and 30 days, kratom extract did not decrease the intestinal transit time indicating that adaptation had occurred. Kratom extract at a dose level of 200 and 400 mg/kg for 30 days and morphine at 3 mg/kg (i.p.) caused a decrease in the increment of body weight that was significantly different from the control and kratom extract at lower doses (50 and 100 mg/kg). However it had no effect on the level of plasma cholecystokinin. The results suggested that methanolic kratom extract exhibited its antidiarrheal effect on rat gastrointestinal tract. The effects may occur via pathways in addition to the action on opioid receptors. High does of kratom extract decreased the increment of body weight similar to the effect of morphine.

Topics: Animals; Antidiarrheals; Body Weight; Cholecystokinin; Gastrointestinal Transit; Medicine, East Asian Traditional; Mitragyna; Naloxone; Plant Extracts; Plant Leaves; Rats; Rats, Wistar

The objective of this study was to quantify and compare the effects of sow's milk and 2 milk replacer diets (containing clotting or non-clotting protein sources) on exocrine pancreatic secretion, plasma cholecystokinin, and immunoreactive cationic trypsin in pigs. In addition, the relationship between exocrine pancreatic secretion and growth in milk-fed pigs was studied. In a changeover experiment, 9 chronically catheterized pigs of 6.6 +/- 0.19 kg of BW were studied for 3 wk. Pigs were assigned to each of 3 diets. Exocrine pancreatic secretion was measured from the third to the seventh day on each diet. The protein content and trypsin activity of the pancreatic juice were measured. Blood samples were taken at 10 min before and after milk ingestion and were analyzed for cholecystokinin and immunoreactive cationic trypsin. Pancreatic protein and trypsin secretion did not differ between pigs fed sow's milk and those fed milk replacer, but the volume secreted was less for the pigs fed sow's milk (0.75 vs. 1.03 mL x kg(-1) x h(-1); P < 0.01). A postprandial response to milk intake was not observed. The 2 milk replacer diets did not affect exocrine pancreatic secretion differently. The average exocrine pancreatic secretion (volume, 0.94 mL x kg(-1) x h(-1); protein, 4.28 mg x kg(-1) x h(-1); trypsin, 1.65 U x kg(-1) x h(-1)) was intermediate between literature values for suckling and weaned pigs. Plasma cholecystokinin was elevated (approximately 18 pmol x L(-1)) and showed low correlations with the pancreatic secretion traits. Plasma immunoreactive cationic trypsin was not significantly related to any of the pancreatic secretion traits and should therefore not be used as an indicator for exocrine pancreatic function in milk-fed pigs. Exocrine pancreatic secretion varied substantially among individual pigs (protein, 0.22 to 13.98 mg x kg(-1) x h(-1)). Pancreatic protein and trypsin secretion showed a positive, nonlinear relationship with performance traits. It was concluded that neither specific sow's milk ingredients nor the protein source are responsible for a low pancreatic protein secretion in suckling pigs. Exocrine pancreatic secretion was positively correlated with ADG in pigs at an identical milk intake.

Topics: Animal Feed; Animals; Animals, Suckling; Body Weight; Cholecystokinin; Diet; Linear Models; Milk; Milk Substitutes; Pancreas, Exocrine; Pancreatic Juice; Swine; Trypsin

Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS.

Topics: Adolescent; Area Under Curve; Biopsy; Body Mass Index; Body Weight; Child; Cholecystokinin; Ghrelin; Humans; Insulin; Male; Obesity; Peptide Hormones; Peptide YY; Prader-Willi Syndrome; Time Factors

Compelling evidence suggests that serotonin (5-HT) is necessary for the refined organization of the cerebral cortex. Here we sought to analyse the short- and long-term consequences of embryonic 5-HT depletion on the development of the cerebral neocortex of the rat. We focused on the migration and differentiation of the pyramidal (projection) and nonpyramidal (interneuron) neuronal populations. Our paradigm used daily injection of DL-P-chlorophenylalanine (PCPA), a reversible inhibitor of 5-HT synthesis, during the E12-17 stage of embryonic development, when major events in corticogenesis take place. We monitored the 5-HT depletion induced by this treatment and showed that it led to subtle alterations in both the pyramidal and nonpyramidal neuronal populations. We found that E12-17 PCPA treatment altered the maturation of pyramidal neurons of layers III and V of the somatosensory cortex, with these cells displaying reduced dendritic arborization and complexity. These long-lasting alterations were not associated with modification of cortical BDNF levels at postnatal stages. We also showed that PCPA treatment transiently altered the incorporation in the cortical plate of interneurons derived from the caudal ganglionic eminence, and persistently affected the differentiation of a subpopulation expressing calretinin and/or cholecystokinin.

Topics: Animals; Blotting, Western; Body Weight; Brain-Derived Neurotrophic Factor; Calbindin 2; Cell Count; Cell Differentiation; Cell Movement; Cell Proliferation; Cerebral Cortex; Cholecystokinin; Female; Fenclonine; gamma-Aminobutyric Acid; Immunohistochemistry; Interneurons; Organ Size; Pregnancy; Pyramidal Cells; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein G; Serotonin; Serotonin Agents

To establish the therapeutic potential of proteasome inhibition, we examined the therapeutic effects of MG132 (Z-Leu-Leu-Leu-aldehyde) in an experimental model of acute pancreatitis.. Pancreatitis was induced in rats by two hourly intraperitoneal (ip) injections of cholecystokinin octapeptide (CCK; 2 x 100 microg/kg) and the proteasome inhibitor MG132 (10 mg/kg ip) was administered 30 min after the second CCK injection. Animals were sacrificed 4 h after the first injection of CCK.. Administering the proteasome inhibitor MG132 (at a dose of 10 mg/kg, ip) 90 min after the onset of pancreatic inflammation induced the expression of cell-protective 72 kDa heat shock protein (HSP72) and decreased DNA-binding of nuclear factor-kappaB (NF-kappaB). Furthermore MG132 treatment resulted in milder inflammatory response and cellular damage, as revealed by improved laboratory and histological parameters of pancreatitis and associated oxidative stress.. Our findings suggest that proteasome inhibition might be beneficial not only for the prevention, but also for the therapy of acute pancreatitis.

Topics: Acute Disease; Animals; Body Weight; Cholecystokinin; Cysteine Proteinase Inhibitors; Cytokines; HSP72 Heat-Shock Proteins; Leupeptins; Male; NF-kappa B; Organ Size; Oxidative Stress; Pancreas; Pancreatitis; Peroxidase; Proteasome Inhibitors; Rats; Rats, Wistar

Cholecystokinin (CCK) and gastrin-releasing peptide (GRP) are gastrointestinal peptides thought to be important regulators of intake and digestion of food in vertebrates. In this study, pre- and postprandial plasma levels of CCK and GRP were measured in rainbow trout (Oncorhynchus mykiss) by the establishment of homologous radioimmunoassays, and the hormonal levels assessed in relation to dietary lipid:protein ratio and food intake. Fish were acclimated to either a high protein/low lipid diet (HP/LL diet; 14.1% lipids) or a normal protein/high lipid diet (NP/HL diet; 31.4% lipids). On three consecutive sampling days, radio-dense lead-glass beads were included in the diets for assessment of feed intake. Fish were terminally sampled for blood and stomach contents prior to feeding at time 0, and at 0.3, 1, 2, 4, 6, and 24 h after feeding. There was a postprandial elevation of plasma CCK levels, which was most evident after 4 and 6 h. Fish fed the NP/HL diet had higher plasma CCK levels compared with those fed the HP/LL diet. Plasma CCK levels were not affected by the amount of food ingested. GRP levels in plasma were not influenced by sampling time, diet, or feed intake. The results indicate that the endocrine release of gastrointestinal CCK is increased during feeding and may be further influenced by the dietary lipid:protein ratio in rainbow trout. Plasma GRP levels, on the other hand, appear not to be influenced by feeding or diet composition.

Topics: Animals; Body Composition; Body Weight; Cholecystokinin; Diet; Feeding Behavior; Female; Gastrin-Releasing Peptide; Oncorhynchus mykiss; Radioimmunoassay; Time Factors

Several mechanisms involved in ingestive behavior and neuroendocrine activity rely on vagal afferent neuronal signaling. Seemingly contradictory to this idea are observations that vagal afferent neuronal ablation by neonatal capsaicin (CAP) treatment has relatively small effects on glucose homeostasis and long-term regulation of energy balance. It may be proposed that humoral endocrine factors and/or their sensitivities compensate for the loss of vagal afferent information, particularly when subjects face disturbances in ambient fuel levels. Therefore, male adult rats neonatally treated with CAP or with the vehicle (VEH) underwent intravenous glucose tolerance tests (IVGTTs) during which blood fuel levels, and circulating adipose, pancreatic, and adrenal hormones were assessed. CAP rats displayed similar hyperglycemia as VEH rats, but with markedly reduced plasma insulin and corticosterone responses. These results indicate that CAP rats have increased insulin sensitivity during hyperglycemic episodes, and lower plasma levels of corticosterone in CAP rats relative to VEH rats could underlie this effect. After the IVGTT, CAP rats had increased plasma adiponectin and reduced plasma resistin levels, and these alterations in adipose hormones might be relevant for post-ingestive metabolic processes. In a second experiment, anorexigenic efficacies of cholecystokinin and leptin were assessed. While VEH rats, but not CAP rats, responded with reduced food intake to i.p. injected cholecystokinin, only CAP rats responded to i.v. infused leptin with a reduction in food intake. It is concluded that reduced HPA axis activity and/or increased leptin signaling could underlie compensations in fuel handling and energy balance following CAP treatment.

Topics: Adiponectin; Animals; Animals, Newborn; Body Weight; Capsaicin; Cholecystokinin; Corticosterone; Eating; Energy Metabolism; Fatty Acids, Nonesterified; Glucose; Glucose Tolerance Test; Homeostasis; Insulin; Leptin; Male; Rats; Rats, Wistar; Time Factors

Neuropeptide Y (NPY) conjugated to saporin (NPY-SAP), a ribosomal inactivating toxin, is a newly developed compound designed to selectively target and lesion NPY receptor-expressing cells. We injected NPY-SAP into the basomedial hypothalamus (BMH), just dorsal to the arcuate nucleus (ARC), to investigate its neurotoxicity and to determine whether ARC NPY neurons are required for glucoprivic feeding. We found that NPY-SAP profoundly reduced NPY Y1 receptor and alpha MSH immunoreactivity, as well as NPY, Agouti gene-related protein (AGRP), and cocaine and amphetamine-related transcript mRNA expression in the BMH. NPY-SAP lesions were localized to the injection site with no evidence of retrograde transport by hindbrain NPY neurons with BMH terminals. These lesions impaired responses to intracerebroventricular (icv) leptin (5 microg/5 microl x d) and ghrelin (2 microg/5 microl), which are thought to alter feeding primarily by actions on ARC NPY/AGRP and proopiomelanocortin/cocaine and amphetamine-related transcript neurons. However, the hypothesis that NPY/AGRP neurons are required downstream mediators of glucoprivic feeding was not supported. Although NPY/AGRP neurons were destroyed by NPY-SAP, the lesion did not impair either the feeding or the hyperglycemic response to 2-deoxy-D-glucose-induced blockade of glycolysis use. Similarly, responses to glucagon-like peptide-1 (GLP-1, 5 microg/3 microl icv), NPY (5 microg/3 microl icv), cholecystokinin octapeptide (4 microg/kg ip), and beta-mercaptoacetate (68 mg/kg ip) were not altered by the NPY-SAP lesion. Thus, NPY-SAP destroyed NPY receptor-expressing neurons in the ARC and selectively disrupted controls of feeding dependent on those neurons but did not disrupt peptidergic or metabolic controls dependent upon circuitry outside the BMH.

Topics: Agouti-Related Protein; alpha-MSH; Amphetamines; Animals; Arcuate Nucleus of Hypothalamus; Binding, Competitive; Body Weight; Catecholamines; Cholecystokinin; Cocaine; Dopamine Uptake Inhibitors; Ghrelin; Glucagon; Glucagon-Like Peptide 1; Hypothalamus; Immunohistochemistry; In Situ Hybridization; Inhibitory Concentration 50; Intercellular Signaling Peptides and Proteins; Leptin; Ligands; Male; Models, Biological; Neurons; Neuropeptide Y; Peptide Fragments; Peptide Hormones; Peptides; Plant Proteins; Pro-Opiomelanocortin; Protein Binding; Protein Precursors; Proteins; Rats; Rats, Sprague-Dawley; Rhombencephalon; RNA, Messenger; Thioglycolates; Time Factors; Toxins, Biological

Ca2+ signaling and exocytosis are highly polarized functions of pancreatic acinar cells. The role of cellular architecture in these activities and the capacity of animals to tolerate aberrant acinar cell function are not known. A key regulator of acinar cell polarity is Mist1, a basic helix-loop-helix transcription factor. Ca2+ signaling and amylase release were examined in pancreatic acini of wild type and Mist1 null mice to gain insight into the importance of cellular architecture for Ca2+ signaling and regulated exocytosis. Mist1-/- acinar cells exhibited dramatically altered Ca2+ signaling with up-regulation of the cholecystokinin receptor but minimal effect upon expression of the M3 receptor. However, stimulation of inositol 1,4,5-trisphosphate production by cholecystokinin and carbachol was inefficient in Mist1-/- cells. Although agonist stimulation of Mist1-/- cells evoked a Ca2+ signal, often the Ca2+ increase was not in the form of typical Ca2+ oscillations but rather in the form of a peak/plateau-type response. Mist1-/- cells also displayed distorted apical-to-basal Ca2+ waves. The aberrant Ca2+ signaling was associated with mislocalization and reduced Ca2+ uptake by the mitochondria of stimulated Mist1-/- cells. Deletion of Mist1 also led to mislocalization of the Golgi apparatus and markedly reduced digestive enzyme content. The combination of aberrant Ca2+ signaling and reduced digestive enzyme content resulted in poor secretion of digestive enzymes. Yet, food consumption and growth of Mist1-/- mice were normal for at least 32 weeks. These findings reveal that Mist1 is critical to normal organelle localization in exocrine cells and highlight the critical importance of maintaining cellular architecture and polarized localization of cellular organelles in generating a propagating apical-to-basal Ca2+ wave. The studies also reveal the spare capacity of the exocrine pancreas that allows normal growth and development in the face of compromised exocrine pancreatic function.

Topics: Amylases; Animals; Basic Helix-Loop-Helix Transcription Factors; Body Weight; Calcium; Carbachol; Cholecystokinin; Cytosol; Dose-Response Relationship, Drug; Exocytosis; Feeding Behavior; Gene Deletion; Golgi Apparatus; Immunoblotting; Immunohistochemistry; Inositol 1,4,5-Trisphosphate; Membrane Potentials; Mice; Mice, Transgenic; Mitochondria; Pancreas; Receptor, Muscarinic M3; Receptors, Cholecystokinin; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Time Factors; Transcription Factors; Trypsin; Up-Regulation

Scintigraphic gastric emptying studies are far from conclusive in obesity. The aim was to investigate gastric emptying and CCK release in weight-stable obese subjects on their usual diet and to study the impact of factors known to determine gastric emptying. Patients entering a weight reduction program were asked to participate in a study examining gastric emptying by scintigraphy and CCK release in response to a meal with questionnaires on feelings of satiety. Forty-five patients (9 M, 36 F) with a mean (SD) BMI of 37.0 (4.0) kg/m2 entered the study. The mean T50 (emptying of 50%) of fluids was 20.7 (10.3) min, and that of solids 141.9 (168.3) min. The percentage emptying of solids was 34.5 (19.9)%/hr. CCK values peaked within 42 min and paralleled the subjective ratings of satiety but did not correlate with gastric emptying. Five of 45 subjects (11%) had very prolonged gastric emptying of solids; they showed higher caloric intakes and higher insulin levels. They did not differ in CCK values and ratings of satiety but scored higher in being active and awake. Without these five subjects the T50 of solids was 94.3 (36.1) min, and the percentage of emptying 37.9 (18.4)%/hr. Liquid emptying was faster and solid emptying similar compared with those of normal-weight individuals. Height, fat-free mass, and waist-hip circumference were positively related to solid emptying. In weight-stable obese subjects liquid emptying was faster and solid emptying similar to those in normal-weight subjects. Higher caloric intakes and insulin levels were present in subjects with prolonged solid emptying; they also appeared more vigilant. Body size and composition were the only determinants suggesting a faster solid emptying in taller and muscular subjects or in subjects with more intraabdominal fat.

Topics: Adult; Body Weight; Cholecystokinin; Female; Gastric Emptying; Humans; Male; Middle Aged; Obesity; Radionuclide Imaging; Satiety Response; Time Factors

Keeping in mind the increased pain complaints reported in anxious or depressive patients, our goal was to investigate in rats the consequences of an experimentally provoked state of anxiety/depression on pain behavior and on its underlying mechanisms. We therefore used a model of social defeat consisting of a 30 min protected confrontation followed by a 15 min physical confrontation, repeated during 4 d, that elicited symptoms close to those observed in humans with anxiety or depression. Indeed, 5 d later, animals subjected to social-defeat confrontation were characterized by a decrease of sweet-water consumption and of body weight, and a hyperactivity of the hypothalamic-pituitary-adrenal axis, suggesting that the social-defeat procedure induced a prolonged state of anxiety. Rats subjected to the social-defeat procedure showed an enhanced nociceptive behavior to the subcutaneous administration of formalin, 5 d after the last confrontation session. Because chronic treatment with the established anxiolytic chlordiazepoxide (10 mg.kg(-1).d(-1)) prevented hyperalgesia, this strongly suggested that this experimental procedure might be a suitable animal model of "anxiety-induced hyperalgesia." Hyperalgesia associated with anxiety not only was related to a significant increase of CCKLM [cholecystokinin (CCK)-like material] in frontal cortex microdialysates but also was prevented by a CCK-B receptor antagonist [4-[[2-[[3-(1H-indol-3-yl)-2-methyl-1-oxo-2[[(tricyclo[3.3[12,17]dec-2-yloxy)-carbonyl]amino]-propyl]amino]-1-phenyethyl]amino]-4-oxo-[R-(R*, R*)]-butanoate N-methyl-D-glucamine (CI-988)] (2 mg/kg), strongly supporting the involvement of central CCKergic systems in these phenomena. Finally, combined treatments with CI-988 and morphine completely suppressed pain-related behavior, supporting the idea that the association of both compounds might represent a new therapeutic approach to reduce the increase of pain complaints highly prevalent among anxious or depressive patients.

Topics: Animals; Anxiety; Body Weight; Cerebral Cortex; Cholecystokinin; Hyperalgesia; Male; Pain Measurement; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin

Brain-derived neurotrophic factor (BDNF) has recently been implicated as an anorexigenic factor in the central control of food intake. Previous studies focused on the hypothalamus as a probable site of action for this neurotrophin. It was demonstrated that BDNF is an important downstream effector of melanocortin signaling in the ventromedial hypothalamus. In this study, we addressed whether BDNF can modulate food intake in the hindbrain autonomic integrator of food intake regulation, i.e. the dorsal vagal complex (DVC). To this end, we used two complementary methodological approaches in adult rats. First, we measured the effects of intraparenchymal infusions of exogenous BDNF within the DVC on food intake and body weight. Second, we measured the endogenous BDNF protein content in the DVC and hypothalamus after food deprivation, refeeding, or peripheral treatments by the anorexigenic hormones leptin and cholecystokinin (CCK). BDNF infusion within the DVC induced anorexia and weight loss. In the DVC, BDNF protein content decreased after 48 h food deprivation and increased after refeeding. Acute and repetitive peripheral leptin injections induced an increase of the BDNF protein content within the DVC. Moreover, peripheral CCK treatment induced a transient increase of BDNF protein content first in the DVC (30 min after CCK) and later on in the hypothalamus (2 h after CCK). Taken together, these results strongly support the view that BDNF plays a role as an anorexigenic factor in the DVC. Our data also suggest that BDNF may constitute a common downstream effector of leptin and CCK, possibly involved in their synergistic action.

Topics: Animal Feed; Animals; Anorexia; Body Weight; Brain Stem; Brain-Derived Neurotrophic Factor; Cholecystokinin; Drinking; Drug Synergism; Eating; Food Deprivation; Humans; Hypothalamus; Injections; Leptin; Male; Rats; Rats, Wistar; Recombinant Proteins; Time Factors; Vagus Nerve

In mammals, including humans, a brain-gut hormone, cholecystokinin (CCK) mediates the satiety effect via CCK-A receptor (R). We generated CCK-AR gene-deficient (-/-) mice and found that the daily food intake, energy expenditure, and gastric emptying of a liquid meal did not change compared with those of wild-type mice. Because CCK-AR(-/-) mice show anxiolytic status, we examined the effects of restraint stress. Seven hours of restraint stress was found to significantly decrease both body weight and food intake during the subsequent 3 days in all tested animals. On the fourth day after restraint stress, the CCK-AR(-/-) mice showed a significantly higher level of daily food intake than prior to stress, and food intake recovered to prestress levels in the wild-type mice. Since peripheral CCK-AR has been known to mediate gastric emptying, both gastric emptying and gastric acid secretion were determined to examine the mechanism of overeating in CCK-AR(-/-) mice. Neither gastric emptying nor gastric acid secretion differed between CCK-AR(-/-) and wild-type mice on the fourth day after stress. In contrast, however, the contents of dopamine and its metabolites in the cerebral cortex of CCK-AR(-/-) mice were increased by stress, but were rather decreased in wild-type mice. Changes in 5-hydroxytryptamine (5-HT) and its metabolite 5HIAA did not differ between the genotypes. In conclusion, CCK-AR(-/-) mice showed overeating after restraint stress, and dopaminergic hyperfunction in the brain of these mice was observed. The present evidence suggests that the CCK-AR function, possibly via altering the dopaminergic function, might be involved in overeating after stress.

Topics: Animals; Body Weight; Cholecystokinin; Eating; Gastric Acid; Gastric Emptying; Hormone Antagonists; Humans; Hyperphagia; Mice; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Sincalide

To investigate the effects of lithium on brain development, leaning and memory, we observed the effects of lithium chloride on rat body weight, learning ability and memory capacity.. Wistar rats were randomly divided into control group and four lithium chloride (LiCl) groups. Four LiCl groups were feed with food containing 3, 30, 300, 3000 mg/kg LiCl respectively. Control group was feed with normal food. By means of measuring the body weight, using Y-maze test and ABC immunohistochemistry, we observed the difference of the body weight gains and Y-maze training times of different groups, and the changes of CCK positive neurons in hippocampus.. Compared with control group, 3, 30 mg/kg LiCl groups could increase the body weight and improve the ability of learning and memory of rats(P < 0.01), however, these of the rats of 300, 3000 mg/kg group were lower (P < 0.05). The numbers of CCK positive neurons in hippocampus of 3, 30, 300 mg/kg groups were significantly increased compared with control group (P < 0.05), that of 3000mg/kg group was lower than control group (P < 0.05).. Low dose of lithium can improve the growth, the learning ability and the memory capacity obviously, but high dose of lithium could result in harmful effects.

Topics: Animals; Body Weight; Cholecystokinin; Dose-Response Relationship, Drug; Hippocampus; Learning; Lithium; Male; Maze Learning; Memory; Random Allocation; Rats; Rats, Wistar

Numerous studies have established the pancreatic B-cell hormone amylin as an important anorectic peptide affecting meal-ending satiety. In the present study, we investigated the effect of a chronic infusion of the amylin antagonist AC 187 on food intake. The studies were performed using obese Zucker fa/fa rats, which are hyperamylinemic but have a defective leptin and insulin signaling system. A chronic intraperitoneal infusion of the amylin antagonist AC 187 (10 microg/kg/h) significantly increased dark phase and total food intake in Zucker but not in lean control rats. During the 8-day infusion experiment, AC 187 had no clear effect on body weight gain in either group. After acute administration, amylin and its agonist salmon calcitonin (sCT) equally reduced food intake in Zucker and lean control rats while cholecystokinin's (CCK) anorectic effect was weaker in the Zucker rats. We provide evidence for amylin being a potential long-term regulator of food intake because AC 187 increased food intake in obese fa/fa rats but not in lean control animals, which have low baseline amylin levels. Amylin may play some role as lipostatic feedback signal similar to leptin and insulin at least when the leptin and insulin feedback signaling systems are deficient. Despite basal hyperamylinemia in the Zucker rats, they do not seem to be less sensitive to the anorectic effects of amylin or its agonist sCT than respective controls. This contrasts with CCK whose anorectic action is reduced in Zucker rats when compared with lean controls.

Topics: Amyloid; Animals; Body Weight; Calcitonin; Cholecystokinin; Eating; Food Deprivation; Infusion Pumps; Infusions, Parenteral; Islet Amyloid Polypeptide; Male; Peptide Fragments; Peptides; Rats; Rats, Zucker; Receptors, Islet Amyloid Polypeptide; Receptors, Peptide; Stimulation, Chemical

Obesity is associated with diabetes and gallstone formation. Obese leptin-deficient (Lepob) and leptin-resistant (Lepdb) mice are hyperglycemic and have enlarged gallbladders with diminished response in vitro to cholecystokinin (CCK) and acetylcholine (ACh). Whether this phenomenon is secondary to hyperosmolar myocytes and/or decreased neuromuscular transmission remains unclear. We hypothesize that myocytes from Lepob and Lepdb obese mice would not respond normally to neurotransmitters.. Cholecystectomy was performed on 39 lean, 19 Lepob, and 20 Lepdb 12-week-old female mice. The gallbladder was divided and enzymatically digested. Half of each gallbladder's myocytes had contraction induced by CCK (10(-8) mol/L, n = 38) or ACh (10(-5) mol/L, n = 40).. Body weights, gallbladder volumes, and serum glucoses were greater for Lep(ob) and Lepdb mice compared to controls (P < .001). Resting myocyte lengths from Lepob and Lepdb mice were 93% and 91% of the length of controls (P < .001). In response to CCK, lean myocytes shortened 6% (P < .01), while myocytes from obese mice demonstrated no shortening. None of the myocytes demonstrated significant shortening with ACh.. These data suggest that gallbladder myocytes from obese mice are (1) foreshortened and (2) have a diminished response to cholecystokinin. We conclude that altered leptin and/or increased glucose may foreshorten myocytes and decrease response to cholecystokinin.

Topics: Acetylcholine; Animals; Blood Glucose; Body Weight; Cholecystokinin; Diabetes Mellitus; Female; Gallbladder; Leptin; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle Contraction; Myocytes, Smooth Muscle; Obesity

The effects of juice from Morinda citrifolia (noni) on gastric emptying, gastrointestinal transit, and plasma level of cholecystokinin (CCK) in rats were studied. Male rats were given noni by gavage at levels of 0.25, 1, or 4 ml/kg once per day for one or 7 days. The rats in the control group were given water, while the rats in the experimental group were fasted overnight before measurement of gastrointestinal motility. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal (10%) and Na251CrO4 (0.5 microCi/ml). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Then, gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Finally, blood samples were collected for measurement of CCK by radioimmunoassay. The administration of noni at 0.25 ml/kg, but not at 1 ml/kg and 4 ml/kg, for 1 day significantly inhibited gastric emptying. In contrast, gastric emptying was significantly inhibited by oral noni (0.25, 1, or 4 ml/kg) for 7 days. Intraperitoneal injection of lorglumide (5 or 10 mg/kg), a selective CCK1 receptor antagonist, effectively attenuated the noni-induced inhibition of gastric emptying. The intestinal transit and body weight, food intake, water intake, urine volume as well as feces weight were not altered by the administration of noni either acutely or chronically, but the administration of oral noni (1 ml/kg) for 7 days increased the level of plasma CCK in male rats. These results suggest that oral noni inhibits gastric emptying in male rats via a mechanism involving stimulation of CCK secretion and CCK1 receptor activation.

Topics: Animals; Beverages; Body Weight; Cholecystokinin; Drinking; Eating; Gastric Emptying; Gastrointestinal Motility; Hormone Antagonists; Male; Metabolism; Morinda; Proglumide; Rats; Rats, Sprague-Dawley

We investigated the changes in the capacity for synthesis of the exocrine pancreas of piglets during the 2 wk after weaning at 7 d of age (trial 1) by measuring the expression of digestive enzymes at mRNA and activity levels in pancreas homogenates, and the effects of high and low feed intakes during the 1st wk postweaning (trial 2) on these measures. The trypsin mRNA level was transiently decreased 43% 3 d postweaning (P < 0.05). Thereafter, trypsin and lipase mRNAs linearly increased (P < 0.05). During the 1st wk postweaning, trypsin- and lipase-specific activities were reduced 44 and 79% (P < 0.05), respectively, whereas 14 d after weaning, trypsin was at the preweaning value and lipase was at a low level. Amylase-specific activity did not change with weaning. Plasma cholecystokinin (CCK) and gastrin concentrations decreased 1 d postweaning and increased afterward up to 3 and 5 d postweaning, respectively. By 3 d after weaning, the mRNA level of trypsin was twofold higher (P < 0.05) in piglets that consumed more feed than in those that consumed less, whereas 7 d after weaning, the groups did not differ. By 7 d after weaning, the specific activity of amylase was higher, and lipase-specific activity was lower, in piglets that consumed more feed than in those that consumed less. Plasma CCK and gastrin concentrations measured 7 d after weaning were correlated with feed intake (r = +0.56 and r = +0.68, P < 0.05, respectively). In conclusion, by 3 d postweaning, pancreatic exocrine function was adapting to the new diet. Afterward, the expression of specific genes coding digestive enzymes and the levels of pancreatic enzyme activities were restored or stimulated, except for lipase-specific activity. Therefore, the pancreas can adjust to weaning and dry food intake as early as wk 2 of life.

Topics: Aging; Animals; Body Weight; Cholecystokinin; Eating; Female; Gene Expression Regulation, Enzymologic; Lipase; Male; Pancreas; Pancreatin; RNA, Messenger; Swine; Trypsin; Weaning

The mouse W/Wv mutation of the c-Kit receptor causes extensive loss of gastrointestinal interstitial cells of Cajal and vagal intramuscular arrays (IMAs; one of the two putative mechanoreceptors in gastrointestinal smooth muscle). To characterize the behavioral phenotype of the c-Kit mouse and to evaluate the roles of these mechanoreceptors in controlling food intake, meal patterns and daily intakes of W/Wv mice and controls were examined using solid (20-mg pellets) and liquid (Isocal) maintenance diets. After the meal pattern experiments, CCK (0.5, 1, 2, 4, 8, and 16 microg/kg ip) was administered to examine the role of the interstitial cells and vagal IMA mechanoreceptors in relaying peripheral signals of satiety activated by CCK-A receptors, whereas the specificity of the response was assessed with the antagonist devazepide (300 microg/kg ip). On both diets, the W/Wv mice ate smaller meals for shorter durations, with a compensatory increase in meal number, resulting in daily intakes and body weights similar to the controls. After CCK injections, the mutant mice consistently suppressed intake more ( approximately 2x) in 30-min tests, regardless of the test diet (12.5% glucose, chow, pellets, and Isocal). The increased sensitivity of W/Wv mice to CCK reflected an increased potency of the hormone (c-Kit mouse ED50 = 2.4 microg/kg; control ED50 = 6.4 microg/kg) and a shift of the dose-response curve to the left. Devazepide blocked the CCK suppression of ingestion. These results indicate that the selective loss of the interstitial cells and IMAs disrupts short-term feeding of the W/Wv mice by inducing an earlier satiety, possibly by altering gastric accommodation and/or emptying, without affecting the long-term mechanisms controlling overall intake or body weight. The results also suggest that the reduction of interstitial cells and IMAs augments the sensitivity to or increases the efficiency of exogenous CCK.

Topics: Animals; Body Weight; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Eating; Enteric Nervous System; Feeding Behavior; Gastric Emptying; Gastrointestinal Motility; Hormone Antagonists; Male; Mice; Mice, Mutant Strains; Phenotype; Proto-Oncogene Proteins c-kit

Neuropeptide Y (NPY) and cholecystokinin (CCK) are known to play important roles in the response to stress and the control of anxiety. In order to investigate the role of NPY and CCK in chronic mild stress (CMS), an animal model of depression, we examined the effects of CMS on sucrose intake as a measure of anhedonia, and expression of NPY and CCK in the rat brain utilizing immunohistochemistry. Sprague-Dawley rats were exposed to a variety of chronic unpredictable mild stressors for 8 weeks. CMS rats significantly reduced the consumption of sucrose intake and gained body weight more slowly, compared to control rats. CMS dramatically produced a decrease in NPY expression in several diencephalic regions including the parvocellular subregion of the paraventricular hypothalamic nucleus (PVN), the periventricular hypothalamic nucleus (PE), the paraventricular thalamic nucleus (PV) and the arcuate nucleus (ACN). In contrast, CCK-like immunoreactivity throughout these areas was substantially increased in chronic mild stressed rats. These results clearly demonstrated that exposure of chronic mild stress upregulated CCK synthesis and downregulated NPY synthesis within the hypothalamus. The present results demonstrated that there was an inverse relationship between NPY and CCK in mediating stress response in an animal model of depression. These findings suggest that CCK and NPY systems may play important roles in expressing the symptopathology of the chronic stress responses such as depression, abnormality of food intake or anxiety-related disorders.

Topics: Animals; Body Weight; Brain Chemistry; Cholecystokinin; Depression; Eating; Immunohistochemistry; Neuropeptide Y; Rats; Stress, Psychological

Chronic nutritional disorders such as protein malnutrition are associated with delayed gastric emptying and increased postprandial cholecystokinin (CCK) levels. This study investigated the mechanisms involved in gastric emptying adaptation to low-protein diet. Two groups of 12 rats were adapted to a low-protein (LPD) or standard diet (SD) for 3 weeks. As compared to rats fed a SD, in rats adapted to a LPD gastric emptying was delayed, whereas postprandial CCK levels were increased. LPD enhanced antral muscle contractile response to CCK and cerulein without altering response to acetylcholine. This increased contractility was associated with up-regulation of CCK-A receptor mRNA levels in antral muscle. Our data suggest that modulation of gastric emptying after adaptation to a low-protein diet involves up-regulation of both CCK-A receptors and CCK-induced contraction of antral smooth muscle.

Topics: Adaptation, Physiological; Animals; Body Weight; Cholecystokinin; Diet, Protein-Restricted; Dietary Proteins; Gastric Emptying; Male; Muscle Contraction; Rats; Rats, Wistar; Receptors, Cholecystokinin; RNA, Messenger; Time Factors

Bombesin (BN) interacts with two mammalian receptor subtypes termed gastrin-releasing peptide (GRP)-preferring (GRP-R) and neuromedin B (NMB)-preferring (NMB-R) that may mediate the satiety action of BN. We examined the feeding behavior of mice that were deficient in the GRP-R (GRP-R KO) to assess the overall contribution of this receptor subtype in the feeding actions of BN-related peptides. GRP-R KO mice failed to suppress glucose intake in response to systemically administered BN and GRP(18-27), whereas both peptides elicited a potent reduction of intake in wild-type (WT) mice. Neither GRP-R KO nor WT mice suppressed glucose intake following NMB administration. Unlike the impaired responses to BN-like peptides, the feeding inhibitory action of cholecystokinin was enhanced in GRP-R KO mice. Consistent with behavioral results, GRP-R KO mice also exhibited a reduction in c-Fos immunoreactivity in the nucleus of the solitary tract (NTS) and paraventricular nucleus (PVN) following peripheral administration of BN. An evaluation of meal patterns showed that GRP-R KO mice ate significantly more at each meal than WT mice, although total 24 h food consumption was equivalent. A long-term analysis of body weight revealed a significant elevation in GRP-R KO mice compared with WT littermates beginning at 45 weeks of age. These data suggest that the GRP-R mediates the feeding effects of BN-like peptides and participates in the termination of meals in mice.

Topics: Animals; Autoradiography; Body Weight; Bombesin; Brain Chemistry; Cholecystokinin; Eating; Male; Mice; Mice, Knockout; Neurokinin B; Peptide Fragments; Proto-Oncogene Proteins c-fos; Receptors, Bombesin; Satiety Response

Ammonium perfluorooctanoate (APFO) is a processing aid in the production of fluoropolymers that has been shown to have a long half-life in human blood. To understand the potential toxicological response of primates, groups of male cynomolgus monkeys were given daily po (capsule) doses of either 0, 3, 10, or 30 (reduced to 20) mg/kg/day for 26 weeks. Two monkeys from each of the control and 10 mg/kg/day dose groups were observed for 90 days after the last dose. Clinical observations, clinical chemistry, determination of key hormones, gross and microscopic pathology, cell proliferation, peroxisomal proliferation, bile-acid determination, and serum and liver perfluorooctanoate (PFOA) concentrations were monitored. Toxicity, including weight loss and reduced food consumption, was noted early in the study at the 30 mg/kg/day dose; therefore, the dose was reduced to 20 mg/kg/day. The same signs of toxicity developed in 3 monkeys at 20 mg/kg/day, after which treatment of these monkeys was discontinued. One 30/20 mg/kg/day monkey developed the signs of toxicity noted above and a possible dosing injury, and this monkey was sacrificed in extremis on Day 29. A 3 mg/kg/day dose-group monkey was sacrificed in extremis on Day 137 for reasons not clearly related to APFO treatment. Dose-dependent increases in liver weight as a result of mitochondrial proliferation occurred in all APFO-treated groups. Histopathologic evidence of liver injury was not observed at either 3 or 10 mg/kg/day. Evidence of liver damage was seen in the monkey sacrificed in moribund condition at the highest dose. Body weights were decreased at 30/20 mg/kg. PFOA concentrations in serum and liver were highly variable, were not linearly proportional to dose, and cleared to background levels within 90 days after the last dose. A no observable effect level was not established in this study, and the low dose of 3 mg/kg/day was considered the lowest observable effect level based on increased liver weight and uncertainty as to the etiology leading to the moribund sacrifice of one low-dose monkey on Day 137. Other than those noted above, there were no APFO-related macroscopic or microscopic changes, changes in clinical chemistry, hormones, or urinalysis, or hematological effects. In particular, effects that have been associated with the development of pancreatic and testicular toxicity in rats were not observed in this study.

Topics: Acyl Coenzyme A; Animals; Bilirubin; Body Weight; Caprylates; Cell Division; Cholecystokinin; DNA; DNA Replication; Estradiol; Fluorocarbons; Hormones; Liver; Macaca fascicularis; Male; Organ Size; Pancreas; Peroxisome Proliferators; Rats; Subcellular Fractions; Testis

The potential toxicity of dietary soy trypsin inhibitor (TI) was evaluated in neonatal miniature swine. From 1 to 6 weeks of age, two groups of male piglets were artificially reared in an Autosow and automatically fed either TI or control liquid diet. From 6 to 39 weeks of age, these two groups were fed either TI or control chow diet. A third group, sow control (SC), suckled from birth to 6 weeks of age, were also weaned to control chow from 6 to 39 weeks of age. Clinical chemistry and plasma cholecystokinin (CCK) determined at 6, 18, 30 and 39 weeks of age, and serum amylase activity with gross and histopathological analyses of major organs at 6 and 39 weeks of age are reported. TI had no effect on plasma CCK, serum amylase activity, or numerous clinical chemistry values. TI-fed piglets had a larger relative liver weight at 6 weeks of age. Relative pancreas weight decreased with age but was not affected by TI. Gross and histopathological analyses of major organs, except the spleen, were within normal limits. Increased incidence of extramedullary hematopoiesis was noted in the spleen of the TI group at 6 but not at 39 weeks of age. There was no consistent pattern in immunohistochemical foci for secretin, gastrin releasing polypeptide or CCK, and no change in DNA, RNA, mitotic index or nuclear density of pancreatic cells. At 6 weeks of age, TI increased pancreatic protein and amylase activity but not trypsin or chymotrypsin activity. None of the effects suggested that this dose of TI was toxic to either the neonatal or sexually mature miniature male swine.

Topics: Administration, Oral; alpha-Amylases; Amylases; Animal Feed; Animals; Animals, Newborn; Body Weight; Cell Cycle; Cholecystokinin; DNA; Immunohistochemistry; Liver; Male; Pancreas; Plant Proteins; RNA; Soybean Proteins; Swine; Trypsin Inhibitors

Peroxisome proliferator-activated receptors (PPARs) are a family of ligand-activated nuclear transcription factors belonging to the nuclear hormone receptors. Troglitazone, a specific ligand for PPAR-gamma is shown to regulate not only lipids and glucose metabolism, but also cell cycle, differentiation, and apoptosis.. To examine the effect of chronic oral administration of troglitazone on the age-related changes of insulin resistance, plasma CCK levels, and pancreatic growth in normal rats.. A troglitazone-rich diet (0.2%) was given from 12 to 28 weeks of age or from 12 or 28 weeks of age to 72 weeks of age.. Fasting serum glucose concentrations in control rats increased progressively with age, which was almost completely prevented by troglitazone treatment. Serum insulin concentrations and pancreatic insulin content in the control rat markedly increased at 28 weeks of age but decreased at 72 weeks of age. These parameters in troglitazone-treated rats remained at nearly the same concentrations at all ages. Insulin concentration relative to DNA in the control rats increased with age, whereas in the troglitazone-treated rats it remained at nearly the same concentrations throughout the observation periods and was significantly lower than that in the controls. Insulin resistance in control rats showed a great increase at 72 weeks of age, whereas it was nearly the same at all ages in troglitazone-treated rats and was significantly lower than those in the control rats. Plasma cholecystokinin concentrations in control rats slightly but insignificantly increased with age, whereas pancreatic weight decreased age-dependently when corrected for body weight. Although troglitazone treatment appeared to decrease plasma cholecystokinin concentrations compared with those in the control rats, it significantly increased pancreatic weight and prevented age-dependent decrease. Troglitazone treatment significantly increased pancreatic protein and DNA contents, but the protein per DNA ratio, an indicator of cellular size, remained at nearly the same concentrations at all ages. The contour of the islets in the control rats at 72 weeks of age was somewhat irregular with structural disarrangement and fibrosis. Moreover, the islets were separated into small sections (cluster) by fibrosis. Troglitazone treatment prevented or reversed these age-related changes of the islets to those in rats at 12 weeks of age.. Our results indicate that troglitazone stimulates pancreatic growth in the normal rat not only by reducing insulin resistance and improving glucose metabolism, but also by suppressing fibrosis of the islets.

Topics: Aging; Alanine Transaminase; Amylases; Animals; Aspartate Aminotransferases; Blood Glucose; Body Weight; Cholecystokinin; Chromans; Diet; DNA; Eating; Hypoglycemic Agents; Insulin; Insulin Resistance; Liver; Male; Organ Size; Pancreas; Proteins; Rats; Rats, Long-Evans; Receptors, Cytoplasmic and Nuclear; Thiazoles; Thiazolidinediones; Transcription Factors; Troglitazone

In the present study, we tested the hypothesis that a single daily injection of the gut peptide CCK, together with continuous leptin infusion, would produce significantly greater loss of body weight than leptin alone. We found that a single daily intraperitoneal injection of CCK-8 (0.5 microg/kg) significantly enhanced the weight-reducing effects of 0.5 microg/day leptin infused continuously into the lateral ventricle of male Sprague-Dawley rats by osmotic minipump. However, CCK and leptin together did not enhance reduction of daily chow intake. Furthermore, there was no synergistic reduction of 30-min sucrose intake, although a significant main effect of both leptin and CCK was observed on sucrose intake. These results 1) confirm our previous reports of synergy between leptin and CCK on body weight, 2) demonstrate that enhancement of leptin-induced weight loss does not require bolus administration of leptin, and 3) suggest that enhanced body weight loss following leptin and CCK does not require synergistic reduction of food intake by leptin and CCK.

Topics: Animals; Body Weight; Cholecystokinin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Synergism; Eating; Injections, Intraperitoneal; Injections, Intraventricular; Leptin; Male; Rats; Rats, Sprague-Dawley; Time Factors

Tyrosine sulfation is mediated by one of two Golgi isoenzymes, called tyrosylprotein sulfotransferases (TPST-1 and TPST-2). A relatively small number of proteins are known to undergo tyrosine sulfation, including certain adhesion molecules, G-protein-coupled receptors, coagulation factors, serpins, extracellular matrix proteins, and hormones. As one approach to explore the role of these enzymes in vivo and how they might interact in biological systems, we have generated TPST-1-deficient mice by targeted disruption of the Tpst1 gene. Tpst1(+/-) mice appear normal and, when interbred, yield litters of normal size with a Mendelian genetic distribution and an equal sex distribution. Tpst1(-/-) mice appear healthy but have approximately 5% lower average body weight than Tpst1(+/+) controls. In addition, we show that although fertility of Tpst1(-/-) males and females per se is normal, Tpst1(-/-) females have significantly smaller litters because of fetal death between 8.5 and 15.5 days postcoitum. These findings suggest that there are proteins involved in regulation of body weight and reproductive physiology, which require tyrosine sulfation for optimal function that are yet to be described. Our findings also strongly support the conclusion that TPST-1 and TPST-2 have distinct biological roles that may reflect differences in their macromolecular substrate specificity.

Topics: Animals; Body Weight; Cholecystokinin; Chromosome Mapping; Female; Fetal Death; Growth; Litter Size; Male; Mice; Mice, Knockout; Sulfotransferases

Rats maintained on a high-fat (HF) diet exhibit reduced sensitivity to the satiation-producing effect of exogenous CCK. Because more CCK is released in response to HF meals than low-fat (LF) meals, we hypothesized that increased circulating CCK associated with ingestion of HF diets contributes to the development of decreased CCK sensitivity. To test this hypothesis, we implanted osmotic minipumps filled with either NaCl or CCK octapeptide into the peritoneal cavity. Subsequently, we examined the effect of intraperitoneal NaCl or CCK (0.5 microg/kg) injection on 30-min food intake. CCK significantly reduced 30-min food intake less in rats implanted with CCK-releasing minipumps compared with those with NaCl-releasing minipumps. Because dietary protein is a potent releaser of endogenous CCK, we hypothesized that rats adapted to a high-protein (HP) diet might also exhibit reduced sensitivity to exogenous CCK. Therefore, in a second experiment, we examined CCK-induced reduction of food intake in rats maintained on LF and rats maintained on HF or HP. Ingestion of LF stimulates very little endogenous CCK secretion, whereas both HF and HP markedly increase plasma CCK concentrations. Both doses of CCK reduced food intake significantly less in HF and HP rats compared with LF rats. There were no differences in 24-h food intake, body weight, or body fat composition among LF-, HF-, and HP-fed rats. These results are consistent with the hypothesis that sustained elevation of CCK either by infusion of exogenous CCK or by dietary-induced elevation of plasma CCK contributes to the development of reduced sensitivity to exogenous CCK.

Topics: Adipose Tissue; Animals; Body Weight; Cholecystokinin; Dietary Fats; Dietary Proteins; Energy Intake; Infusions, Parenteral; Injections, Subcutaneous; Lipid Metabolism; Male; Rats; Rats, Sprague-Dawley; Satiation; Sincalide

We investigated the effects of a CCK-A receptor antagonist on the development of mother preference. Lambs received 2-NAP either at birth or 6, or 12 h later. Controls were given saline. When tested at 24 h of age, lambs receiving 2-NAP at birth or 6 h later did not display mother preference unlike controls and lambs which were given 2-NAP at 12 h. The effect of the antagonist persisted at 48 h of age in lambs treated at birth. This suggests that endogenous CCK participates in the development of mother preference only in the first few hours following birth.

Topics: Animals; Animals, Newborn; Aspartic Acid; Behavior, Animal; Body Weight; Cholecystokinin; Female; Mothers; Naphthalenesulfonates; Sheep; Time Factors

CCK is a satiety neuropeptide. Animal studies have shown that both acute and chronic exposure to nicotine results in weight loss which is associated with an increase in hypothalamic CCK and that CCK antagonists ameliorate symptoms of nicotine withdrawal. A major detriment to smoking cessation, especially in women, is the fear of gaining weight. These observations suggested that genetic variants in the CCK gene might be a possible risk factor for smoking.. To test this hypothesis we examined the association of the C-45T promoter polymorphism in the Sp1 binding region of the CCK gene with smoking and BMI in two independent groups of subjects.. Group 1 consisted of 191 Caucasian women participating in an obesity study. The T allele was present in 15% of women who had never smoked, 20% of ex-smokers, and 58% of current smokers, P < or = 0.0014. The T allele was present in 26.8% of ever-smokers (ex-smokers + current smokers). There was no association with BMI. Group 2 consisted of 725 parents of twins from the Minnesota Twin and Family Study of substance abuse. Logistic regression analysis showed that a diagnosis of nicotine dependence was significantly associated with the T allele (P < or = 0.002) and with gender (males > females) (P < or = 0.001), but not with BMI (P < or = 0.68). The T allele was present in 15.9% of parents who had never smoked and 24.7% of ever-smokers, very similar to the results for group 1.. These results are consistent with a role of the CCK gene as a risk factor for smoking.

Topics: Adult; Alleles; Body Weight; Chi-Square Distribution; Cholecystokinin; Female; Genetic Predisposition to Disease; Genotype; Humans; Male; Middle Aged; Models, Biological; Obesity; Polymorphism, Genetic; Regression Analysis; Reproducibility of Results; Smoking; Tobacco Use Disorder; White People

We investigated the role of histamine H1 receptors in mediating the anorectic effect of intraperitoneally injected amylin (5 and 20 microg/kg), the amylin agonist salmon calcitonin (sCT; 10 microg/kg), leptin (1.3 mg/kg), and cholecystokinin (CCK; 20 microg/kg). The experiments were performed with mice lacking functional H1 receptors (H1Rko) and wild-type (WT) controls. The mice were also injected with the H3 antagonist thioperamide (20 mg/kg), which reduces feeding by enhancing the release of endogenous histamine through presynaptic H3 receptors. The feeding-suppressive effect of thioperamide was abolished in H1Rko mice. The anorectic effects of amylin and sCT were significantly reduced in 12-h food-deprived H1Rko mice compared with WT mice [1-h food intake: WT-NaCl 0.51 +/- 0.05 g vs. WT-amylin (5 microg/kg) 0.30 +/- 0.06 g (P < 0.01); H1Rko-NaCl 0.45 +/- 0.05 g vs. H1Rko-amylin 0.40 +/- 0.04 g; WT-NaCl 0.40 +/- 0.09 g vs. WT-sCT (10 microg/kg) 0.14 +/- 0.10 g (P < 0.05); H1Rko-NaCl 0.44 +/- 0.08 g vs. H1Rko-sCT 0.50 +/- 0.06 g]. The anorectic effect of leptin was absent in ad libitum-fed H1Rko mice, whereas CCK equally reduced feeding in WT and H1Rko animals. This suggests that the histaminergic system is involved in mediating the anorectic effects of peripheral amylin and sCT via histamine H1 receptors. The same applies to leptin but not to CCK. H1Rko mice showed significantly increased body weight gain compared with WT mice, supporting the role of endogenous histamine in the regulation of feeding and body weight.

Topics: Amyloid; Animals; Anorexia; Body Weight; Calcitonin; Cholecystokinin; Eating; Histamine Antagonists; Islet Amyloid Polypeptide; Leptin; Male; Mice; Mice, Knockout; Pancreas; Piperidines; Receptors, Histamine H1

The objective of this study was to examine the effects of 10% food restriction on body weight, plasma cholecystokinin (CCK) levels, and exocrine pancreatic function in male Sprague-Dawley rats. A matched group of rats with unrestricted access to food served as controls. After ingesting the diets for 32 da, the rats were killed and blood obtained for plasma cholecystokinin, glucose, and insulin determinations. To evaluate pancreatic function, the pancreases were removed, weighed, and digested with collagenase to isolate pancreatic acini, which were incubated with maximal stimulating dose of CCK. The fraction of amylase that was released into the medium was measured. To explore the role of membrane receptors in exocrine pancreatic secretion, CCK receptor affinity and CCK receptor capacity were determined by radioligand binding assays in isolated, purified membranes from pancreatic acini. Compared to the control group, rats with 10% food restriction showed (a) reduced body weight gain, (b) increased pancreatic weight, (c) increased plasma CCK level, and (d) no significant changes in plasma glucose or insulin levels. The food-restricted group showed a reduction of pancreatic function, assessed by measuring amylase release in response to maximal CCK stimulation; the amylase release was diminished by 35% in the food-restricted group. In isolated acinar cell membranes from food-restricted rats, CCK receptor affinity and capacity were reduced by 23% and 16%, respectively, compared to controls. These results indicate that consumption of less food than normal affects pancreatic function by a mechanism that evidently involves CCK release and downregulation of CCK receptors. The data suggest that CCK plays an important physiological role in the adaptation to eating less food, and thereby to the lowering of body weight in rats and, possibly, in other animals.

Topics: Amylases; Animals; Body Weight; Cholecystokinin; Energy Intake; Male; Pancreas; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin

Pancreaticobiliary diversion (PBD) and biliodigestive shunt (BDS) cause long-standing hypercholecystokininemia followed by pancreatic hyperplasia. These changes have been suggested to be due to the lack of intraluminal trypsin and bile, respectively, in the upper small intestine. The aim of these experiments was to study the effect of restoration of intraluminal trypsin and bile on plasma levels of cholecystokinin (CCK) and the changes found in exocrine and endocrine pancreas after PBD and BDS. Male Sprague-Dawley rats were used. PBD was done in 16 rats, eight of which had trypsin dissolved in 50 mM sodium bicarbonate (SB), and eight had SB only by gastric intubation twice daily. BDS was done in another 16 rats, eight of which had bile dissolved in SB, and eight had SB in a similar manner. Sham-operated rats had SB and served as controls. After 4 weeks, the rats were killed, and the concentrations of circulating CCK, gastrin, glucose, glucagon, and insulin were determined. The pancreas was removed, weighed, and analyzed for contents of water, protein, and DNA. In another study, PBD-operated rats got trypsin in varying dosages or trypsin and taurocholate in combination for 2 weeks before death. The concentrations of plasma CCK and glucagon were elevated after both PBD and BDS. PBD decreased the concentration of gastrin in plasma. PBD caused an increase of pancreatic weight and the contents of protein and DNA. Trypsin substitution to PBD-operated rats did not affect plasma CCK or glucagon levels, but the PBD-induced increases in weight and DNA content were counteracted by trypsin. Higher dosages of trypsin did not further influence the effects seen after PBD. Pancreatic weight and DNA content were increased after BDS. Bile administration completely abolished the increase in plasma CCK and glucagon, as well as the gain in pancreatic weight, and reduced the increase in pancreatic DNA. Substitution with bile to BDS-operated rats abolished the increase in the plasma levels of CCK and glucagon, as well as the trophic effects on the pancreas. Trypsin substitution to PBD-operated rats partly reversed the trophic effects on the pancreas but not the hormonal changes in plasma. Thus the trophic effects on the pancreas exerted by BDS seem to be dependent on the lack of bile in the upper small intestine, whereas the effects of PBD only partly are a consequence of the absence of intraluminal trypsin.

Topics: Animals; Bile; Biliopancreatic Diversion; Body Weight; Cholecystokinin; Digestive System Surgical Procedures; Dose-Response Relationship, Drug; Islets of Langerhans; Male; Pancreas; Rats; Rats, Sprague-Dawley; Trypsin

Lipopolysaccharide (LPS) and cholecystokinin (CCK) have been shown to have anorectic properties in a variety of species. The present study examined the effects of LPS and CCK, both alone and in combination, on two different aspects of water ingestion, water intake and palatability. On test days, animals were first injected intraperitoneally (i.p.) with either LPS (200 microg/kg) or NaCl vehicle, and 2 h later received a second injection of either CCK (8 microg/kg) or NaCl vehicle. In Experiment 1, water intake was monitored for 1 h on 3 separate test days 72 h apart; while in Experiment 2, water palatability was assessed using the taste reactivity test (TRT), on two separate test days 72 h apart. Both LPS and CCK significantly (p<0.05) reduced water intake, with the effects of combined LPS with CCK being more pronounced than either agent injected alone. Rats developed a rapid tolerance to the effects of LPS on water intake on subsequent exposures to LPS. Results from the TRT indicated that LPS enhanced water palatability (p<0.05), as evidenced by a high level of ingestive responding, whereas CCK produced a pattern of responding indicative of satiety. LPS plus CCK reduced ingestive responding on the first test day, but these responses were significantly increased on the second test day (p<0.05). These results demonstrate that although LPS reduces water intake, it enhances water palatability. The results further underscore the necessity for examining palatability changes in addition to intake measures when studying the regulation of feeding and drinking.

Topics: Animals; Body Weight; Cholecystokinin; Drinking; Drinking Behavior; Lipopolysaccharides; Male; Rats; Rats, Long-Evans; Taste

Cholecystokinin (CCK) has been suggested to be involved in the development and course of acute pancreatitis. In the present study we measured plasma CCK concentrations in acute experimental pancreatitis (AEP) in the rat, and evaluated the role of circulating CCK levels on the initial pancreatic damage in pancreatitis.. Endogenous hyperCCKemia was induced by surgical biliodigestive shunt (BDS) and exogenous hyperCCKemia by infusion of CCK-8S. The CCK-A receptor antagonist devazepide was used to antagonize the effect of CCK. Pancreatitis was induced by pancreatic duct infusion of sodium taurodeoxycholate 4 wk after the BDS operation or 1 wk after the start of the infusions. Nonpancreatitic sham- and BDS-operated rats, respectively, were used as control animals as were groups of otherwise untreated rats with pancreatitis. The animals were sacrificed 6 h after induction of pancreatitis. Concentrations of CCK were determined in plasma as were protein and amylase levels in the pancreas and peritoneal exudates. The extent of pancreatic necroses was assessed microscopically.. Pancreatitis caused an 11-20-fold increase of circulating CCK as measured after 6 h. In pancreatitic rats with induced hyperCCKemia, there was a further marked increase of plasma CCK. Pancreatic weight and edema, protein and amylase contents, and extent of necroses were the same regardless of the level of plasma CCK. Devazepide had no influence on the studied pancreatic parameters.. We conclude that acute taurodeoxycholate-induced pancreatitis in the rat is associated with elevated plasma CCK concentrations. There seems, however, not to be any correlation between the degree of hyperCCKemia and the extent of initial pancreatic damage.

Topics: Acute Disease; Animals; Body Weight; Cholecystokinin; Male; Pancreatitis; Rats; Rats, Sprague-Dawley; Taurodeoxycholic Acid

Cholecystokinin (CCK) is a hormone with well-known secretory and trophic effects on the pancreas. This also is true for epidermal growth factor (EGF), which acts in a paracrine and autocrine way. The aim was to study the influence of CCK on cell proliferation in rat pancreas with special reference to the expression of EGF, the EGF receptor, and phosphorylated tyrosine. Twenty-four male Sprague-Dawley rats received either one single injection, or injections twice daily for 3 days of 6 microg sulfated CCK-8 (CCK-8S) subcutaneously in the neck. The same number of rats received injections of 1% bovine serum albumin (BSA) in the same way. The rats were killed 1, 3, or 6 hours after the last injection. One hour before killing, they received 50 mg/kg of bromodeoxyuridine (BrdU) intraperitoneally. Plasma was collected for analysis of CCK. The pancreas was dissected, and in situ hybridization using a probe for EGF mRNA was performed for semiquantification of gene expression. Immunocytochemistry using antibodies against the EGF receptor and phosphotyrosine was performed to examine the expression of the proteins, and against BrdU for measuring the cell proliferation. A single injection of CCK-8S led to hyperCCKemia at 1 and 3 hours afterward. After 6 hours, plasma CCK had returned to the same levels as in control rats. The cell proliferation was unaffected. The rats that received CCK-8S injections for 3 days still had hyperCCKemia 6 hours after the last injection. The cell proliferation was increased by CCK, as indicated by the BrdU labeling. However, neither body weight nor pancreatic weight was affected. In controls, EGF was expressed all over the gland, but its receptor and phosphotyrosine were expressed only in ductal cells and in the islet cells of endocrine pancreas. There was no difference in the pancreatic staining of EGF, its receptor, or phosphotyrosine at the different time points studied. There was no difference in the staining of EGF and its receptor between CCK-8S- and BSA-treated animals, but phosphotyrosine staining was detectable in acinar cells after 3 days of CCK-8S injections. Thus CCK-8S causes hyperCCKemia with ensuing enhanced cell proliferation in rat pancreas. This effect on the cell proliferation seems to be a direct effect of CCK and not mediated by changes in the tissue levels of EGF or its receptor.

Topics: Animals; Body Weight; Bromodeoxyuridine; Cholecystokinin; Epidermal Growth Factor; ErbB Receptors; Immunohistochemistry; In Situ Hybridization; Male; Organ Size; Pancreas; Phosphotyrosine; Rats; Rats, Sprague-Dawley

The present study was aimed to test the hypothesis that increased endogenous CCK may interact with the anorectic serotonergic agent dl-fenfluramine to reduce food intake in rats. Previous studies, using selective CCK receptor antagonists, could demonstrate CCK-dependent 5-HT-induced anorexia. In the present approach, we used protease inhibitors to increase levels of endogenous CCK instead of blocking CCK receptors by antagonists. The protease inhibitors we used were soybean trypsin inhibitor (STI) and camostate. We hypothesized that combining the anorectic serotonergic drug dl-fenfluramine with either STI or camostate should result in an enhanced hypophagic effect when compared to single drug treatment. All feeding experiments were performed in non-deprived rats during night time feeding. Given alone, STI (500 mg/kg, po), camostate (200 mg/kg po) and also fenfluramine (1-9 mg/kg ip) reduced significantly food intake, with a more pronounced effect following fenfluramine. However, the experiments do not provide evidence for any additive or synergistic action between camostate or STI and the anorectic serotonergic drug dl-fenfluramine on food intake.

Topics: Animals; Anorexia; Body Weight; Cholecystokinin; Dose-Response Relationship, Drug; Drug Interactions; Eating; Esters; Fenfluramine; Gabexate; Guanidines; Male; Protease Inhibitors; Rats; Rats, Wistar; Selective Serotonin Reuptake Inhibitors; Serotonin; Time Factors; Trypsin Inhibitors

Food intake and body weight are determined by a complex interaction of regulatory pathways. To elucidate the contribution of the endogenous peptide cholecystokinin, mice lacking functional cholecystokinin-A receptors were generated by targeted gene disruption. To explore the role of the cholecystokinin-A receptor in mediating satiety, food intake of cholecystokinin-A receptor-/- mice was compared with the corresponding intakes of wild-type animals and mice lacking the other known cholecystokinin receptor subtype, cholecystokinin-B/gastrin. Intraperitoneal administration of cholecystokinin failed to decrease food intake in mice lacking cholecystokinin-A receptors. In contrast, cholecystokinin diminished food intake by up to 90% in wild-type and cholecystokinin-B/gastrin receptor-/- mice. Together, these findings indicate that cholecystokinin-induced inhibition of food intake is mediated by the cholecystokinin-A receptor. To explore the long-term consequences of either cholecystokinin-A or cholecystokinin-B/gastrin receptor absence, body weight as a function of age was compared between freely fed wild-type and mutant animals. Both cholecystokinin-A and cholecystokinin-B/gastrin receptor-/- mice maintained normal body weight well into adult life. In addition, each of the two receptor-/- strains had normal pancreatic morphology and were normoglycemic. Our results suggest that although cholecystokinin plays a role in the short-term inhibition of food intake, this pathway is not essential for the long-term maintenance of body weight.

Topics: Animals; Body Weight; Cholecystokinin; Eating; Female; Gastrins; Male; Mice; Mice, Knockout; Receptor, Cholecystokinin A; Receptors, Cholecystokinin

The behavioral effects of AR-R 15849, a novel cholecystokinin agonist with high affinity and selectivity for the CCK-A receptor subtype, were examined. Initially, using an operant feeding paradigm to test for anorectic activity and specificity, acute administration of AR-R 15849 was found to alter the intake and pattern of feeding in a manner similar to prefeeding. Further, AR-R 15849 did not induce compensatory feeding as did CCK-8, and did not affect performance on running rates of responding, or motor activity on a running wheel, as did fenfluramine. In tests for subchronic anorectic activity, daily intraperitoneal injections of AR-R 15849 significantly reduced food intake in fasted rats over a 9-day test period with greater efficacy compared to its nonselective predecessor AR-R 14294 (formerly FPL 14294). The sustained decrease in food intake with AR-R 15849 treatment resulted in a significant reduction in body weight gain over 9 days. Finally, an experiment designed to determine the effect of caloric deprivation and subchronic drug exposure on the overall efficacy of AR-R 15849 indicated that pharmacological tolerance does not develop following subchronic treatment.

Topics: Animals; Appetite Depressants; Behavior, Animal; Body Weight; Cholecystokinin; Drug Tolerance; Eating; Fenfluramine; Male; Motor Activity; Rats; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Time Factors

The gut peptide CCK is a nutrient-related signal important to the control of food intake. In the present studies, we observed that a single intraperitoneal injection of CCK (1-2 microgram/kg) given 2-3 h after intracerebroventricular leptin (2-5 microgram) reduced body weight and chow intake over the ensuing 48 h more than did leptin alone. CCK alone had no effect on either 48-h chow intake or body weight but significantly reduced feeding during a 30-min sucrose test. However, reduction of 30-min sucrose intake by CCK was not enhanced by prior intracerebroventricular leptin. The present data suggest that CCK can contribute to the regulation of body weight when central leptin levels are elevated.

Topics: Animals; Body Weight; Cholecystokinin; Drinking; Drug Synergism; Eating; Injections, Intraperitoneal; Injections, Intraventricular; Leptin; Male; Proteins; Rats; Rats, Sprague-Dawley; Solutions; Sucrose; Time Factors

Food intake and meal size are reduced in female Long-Evans rats during estrus. To investigate the contribution of the satiating action of endogenous cholecystokinin (CCK) to this, rats were injected with 1 mg/kg of the potent, selective CCK(A) receptor antagonist, devazepide, during diestrus, when meal size is maximal, and during estrus, when it is minimal. Devazepide increased spontaneous food intake and meal size during estrus, but not during diestrus. Meal frequency was not affected by devazepide treatment. These results indicate that the potency of the CCK satiety-signaling system increases during estrus.

Topics: Animals; Body Weight; Cholecystokinin; Circadian Rhythm; Devazepide; Diestrus; Eating; Estrus; Feeding Behavior; Female; Hormone Antagonists; Motor Activity; Rats; Rats, Long-Evans; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Satiation

The effects of oral administration of two synthetic trypsin inhibitors (camostate and ONO-3403) and soybean trypsin inhibitor (SBTI) on cholecystokinin (CCK), secretin gene expression and pancreatic secretion were examined in CCK-A-receptor-deficient (OLETF) rats. The rats were fed chow containing 0.1% trypsin inhibitors for 7 days. To examine pancreatic secretion, the rats were prepared with cannulae to drain the bile and pancreatic juice separately, a duodenal cannula and an external jugular vein cannula. The animals were maintained in Bollman cages and the experiments were conducted 4 days after surgery. The levels of CCK mRNA were significantly increased by each treatment. The levels of secretin mRNA were significantly increased by camostate and SBTI, but not by ONO-3403. Bicarbonate secretion was significantly increased in rats treated with camostate and ONO-3403, but not SBTI, while protein secretion was not affected by any treatment. These observations suggest that increased bicarbonate secretion produced by synthetic trypsin inhibitors in CCK-A-receptor-deficient rats may not be due to secretin but due to ONO-3403 in the circulation.

Topics: Allylglycine; Animals; Benzamidines; Bicarbonates; Blotting, Northern; Body Weight; Cholecystokinin; Eating; Esters; Gabexate; Gene Expression Regulation; Guanidines; Intestinal Mucosa; Intestines; Pancreas; Pancreatic Juice; Rats; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; RNA, Messenger; Secretin; Trypsin Inhibitor, Kunitz Soybean; Trypsin Inhibitors

The present study examined the effects of repeated injections of lipopolysaccharide (LPS) and cholecystokinin (CCK) on both sucrose palatability and body weight. Rats received repeated injections of LPS (200 microg/kg), CCK (8 microg/kg) and/or NaCl on days 1, 4, 7 and 10. Body weight was monitored on each test day and sucrose palatability was assessed using the taste reactivity test (TRT) on days 7 and 10. Rats treated with LPS developed a rapid tolerance to the reductions in body weight; however, this tolerance did not affect sucrose palatability. Furthermore it was found that repeated exposures to LPS and CCK attenuated the typical satiety related behaviors produced in the TRT by administration of CCK. This desensitization to CCK with repeated exposures to LPS may be one of the mechanisms that could account for the rapid development of tolerance to LPS-induced hypophagia.

Topics: Animals; Behavior, Animal; Body Weight; Cholecystokinin; Drug Tolerance; Injections; Lipopolysaccharides; Male; Rats; Rats, Long-Evans; Satiety Response; Sucrose; Taste; Time Factors

The pancreas is the main target of the trophic effect of cholecystokinin (CCK), with a transient increase in cell proliferation and persistent effect on DNA content and weight gain when given continuously. Whether CCK exerts similar effects on the liver and biliary tract is not known. Most studies on this subject have hitherto been done in the rat. The aim of the present experiments was therefore to study the possible concomitant trophic effects of CCK on these three organs in a gallbladder-bearing animal, the hamster.. CCK-8S or the CCK-A receptor antagonist devazepide were infused subcutaneously by osmotic minipumps for 4 weeks in 11 and 7 hamsters, respectively. Fifteen animals served as untreated controls. One hour before sacrifice tritiated thymidine was injected intraperitoneally. Plasma was collected for determination of CCK and the pancreas, liver, common bile duct and gallbladder were excised. The pancreas and liver were weighed and processed for the contents of protein, DNA and water. Tissue specimens were taken for autoradiography.. The concentration of CCK in plasma increased fourfold during the infusion of CCK-8S. The pancreas and, to a lesser extent, the liver increased in weight, DNA and protein contents after infusion of CCK-8S, whereas the pancreas, but not the liver, decreased in weight and protein content after infusion of devazepide. Pancreatic amylase content was increased after CCK-8S treatment, but unaffected by devazepide. Labelling index of pancreatic acinar cells, hepatocytes and gallbladder epithelium was no different from that of controls after four weeks of infusion of CCK-8S or devazepide. A correlation was found between the concentration of plasma CCK on one hand and the weights and DNA contents in pancreas and liver on the other.. The results suggest that CCK stimulates growth of both the pancreas and the liver in the hamster.

Topics: Animals; Body Weight; Cholecystokinin; Cricetinae; Devazepide; Hormone Antagonists; Liver; Male; Organ Size; Pancreas; Sincalide; Thymidine

The present study evaluates long-term effects of the CCK-agonist caerulein and the CCK-A antagonist loxiglumide in obese and lean Zucker rats. Caerulein and loxiglumide altered food intake neither in obese nor in lean rats. By as yet unknown mechanisms, however, weight increase was accelerated by loxiglumide and reduced by caerulein in obese and lean rats. Caerulein increased pancreatic weight only in lean but not in obese rats. Thus, obese rats show a resistance of pancreatic CCK-A receptors. The failure of CCK-agonist and -antagonist to alter food intake suggests that this CCK-resistance is not responsible for obesity in the genetically altered rats.

Topics: Animals; Body Weight; Ceruletide; Cholecystokinin; Drug Resistance; Eating; Female; Male; Obesity; Organ Size; Pancreas; Proglumide; Rats; Rats, Zucker; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Satiety Response

Otsuka Long-Evans Tokushima Fatty (OLETF) rats develop obesity, hyperglycemia, and non-insulin-dependent diabetes mellitus and do not express cholecystokinin A (CCK-A) receptors, the receptor subtype mediating the satiety actions of CCK. In short-term feeding tests, male OLETF rats were completely resistant to exogenous CCK, and their response to bombesin was attenuated. Comparisons of liquid meal consumption in OLETF and control Long-Evans Tokushima (LETO) rats demonstrated that 1) OLETF rats had greater intakes during 30-min scheduled daytime meals and significantly larger and fewer spontaneous night-time meals and 2) although the initial rates of licking were the same, OLETF rats maintained the initial rate longer and the rate at which their licking declined was slower. In 24-h solid food access tests, OLETF rats consumed significantly more pellets than LETO controls, and this increase was attributable to significant increases in meal size. Together, these data are consistent with the interpretation that the lack of CCK-A receptors in OLETF rats results in a satiety deficit leading to increases in meal size, overall hyperphagia, and obesity.

Topics: Animals; Body Weight; Bombesin; Cholecystokinin; Circadian Rhythm; Eating; Glucose; Male; Obesity; Rats; Rats, Inbred Strains; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Satiation

The neurotoxin DSP-4 has, in this laboratory, previously been shown to upregulate cholecystokinin (CCK) binding in the frontal cortex and the hippocampus in rats. The present study investigated the effect of DSP-4 on CCK peptide levels and CCK receptor binding in some rat brain areas. Sprague-Dawley rats were given single injections of DSP-4 (10 and 50 mg/kg) and examined after 1 week. Wistar rats were given an injection of DSP-4 (50 mg/kg) and evaluated 1 week and 4 months after treatment. No significant changes in CCK levels or in CCK binding were found. It has been found that stress produced by handling of the rats immediately before decapitation can result in an increase in cortical CCK receptor binding. This finding led to the speculation that the upregulation of CCK binding after DSP-4 treatment which was reported earlier, reflects a stress-potentiating effect of DSP-4.

Topics: Adrenergic Agents; Adrenergic alpha-Agonists; Animals; Benzylamines; Body Weight; Brain Chemistry; Cholecystokinin; Male; Neuropeptides; Norepinephrine; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Rats, Wistar; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Receptors, Cholecystokinin

The effect of daily or interval (every 3 d) feeding on body weight change, blood glucose and cholecystokinin (CCK) concentrations, immune function, and behavioral activity were determined during the gestation period of sows. Sows were fed a corn-soybean meal diet either 2 kg daily or 6 kg once every 3rd d (interval). Body weight changes for the 42-d trial period were not different (P > .05) between regimens. Blood glucose concentrations were similar before feeding (P > .05). Two hours after feeding, glucose concentrations increased in interval-fed sows but not in daily-fed sows (P < .05). Premeal plasma CCK concentrations were greater for daily-fed sows than for interval-fed sows (P < .05). The CCK concentrations in sows of both regimens increased after feeding above premeal levels (P < .05), and interval-fed sows exhibited higher concentrations than daily-fed sows (P < .05). Immune function as evaluated through mitogen-induced proliferation of T cells was greater in daily-fed sows than in interval-fed sows (P < .05). Daily-fed sows were more active overall and on any given day than interval-fed sows (P < .05) and thus seemed to expend more energy. Further, daily-fed sows exhibited higher levels of mouth-based activities (i.e., sham chewing, licking, appetitive and consummatory feeding behavior, and excess drinking) than sows restricted to consumption of one large meal every 3rd d. These indicators suggest that feeding motivation significantly affected overall performance of sows. This study emphasizes the need for evaluating the impact of feeding regimens and meal size on feeding motivation and, ultimately, on the well-being of the gestating sows.

Topics: Animals; Arousal; Behavior, Animal; Blood Glucose; Body Weight; Cholecystokinin; Drinking; Eating; Feeding Behavior; Female; Lymphocyte Activation; Motivation; Pregnancy; Pregnancy, Animal; Satiation; Swine; T-Lymphocytes

To measure leptin, insulin and cholecystokinin (CCK) concentrations in obese women on calorie restriction and to determine their correlation with hunger-satiety ratings. Although it has been proposed to play a role in appetite regulation, the effects of physiological concentrations of these hormones on hunger-satiety in humans have not yet been well established.. Prospective metabolic study. A two week 'wash-in period' followed by a three-week observation period, during which each subject underwent six measurements of satiety, blood parameters and body weight.. Energy Metabolism Research Unit, Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.. 22 moderately to severely overweight women (mean age: 45 +/- 8 y; body mass index (BMI): 33 +/- 6 kg/m2).. Energy restriction, in the form of a 3.3 MJ (800 kcal) diet during five weeks.. Fasting blood levels of leptin, insulin, glucose and CCK, fasting hunger-satiety scores and body weight.. The mean (+/- s.d.) fasting serum leptin concentration at the beginning of the observation period was 26.1 +/- 15.9 ng/ml (range: 6.7-59.8 ng/ml). Leptin concentrations correlated positively with body weight (P < 0.0001). Furthermore, reductions in body weight were associated with decreases in fasting leptin levels (P = 0.002). Leptin concentrations correlated with serum levels of insulin (P = 0.0001) and CCK (P = 0.06), but in multivariate analysis including insulin, CCK and glucose, only leptin had a significant relationship with satiety (P = 0.04). This relationship was linear.. These results confirm the association between leptin levels, body weight and serum insulin. We also showed that higher serum leptin levels correlated with greater feelings of fullness, a relationship which was not blunted in the more obese subjects. These findings suggest that leptin is a satiety hormone that reduces appetite, even in obese individuals, and that weight gain must be due to other factors, overriding this feed-back regulation.

Topics: Adult; Appetite; Black People; Body Weight; Cholecystokinin; Female; Humans; Hunger; Insulin; Leptin; Middle Aged; Obesity; Prospective Studies; Proteins; Satiety Response; White People

Abdominal vagal and splanchnic afferents play an important role in the control of food intake in that they transmit various satiety signals to the central nervous system. Inasmuch as previous studies have shown that the anorectic effect of intraperitoneally injected amylin was not abolished by subdiaphragmatic vagotomy, the aim of the present study was to elucidate the role of splanchnic afferents in mediating amylin's anorectic effect after intraperitoneal injection. Rats were pretreated intraperitoneally with the neurotoxin capsaicin, which destroys primary sensory (vagal and splanchnic) afferents. Sham-treated rats served as control. Capsaicin-pretreatment had no influence on the anorectic effects of amylin (5 microg/kg) and the related peptide, calcitonin gene-related peptide (CGRP; 5 microg/kg), in 24-h food-deprived rats. Abolition of cholecystokinin's (3 microg/kg) anorectic effect agrees with previous studies and confirmed the effectiveness of the capsaicin pretreatment. In conclusion, the anorectic effects of intraperitoneally injected amylin and CGRP are not mediated by capsaicin-sensitive primary sensory neurons. Both anorectic peptides are, therefore, most likely to act within the central nervous system. Previous studies suggest that the relevant receptors might be located in neurons of the area postrema-nucleus of the solitary tract region.

Topics: Afferent Pathways; Amyloid; Animals; Body Weight; Calcitonin Gene-Related Peptide; Capsaicin; Cholecystokinin; Eating; Islet Amyloid Polypeptide; Male; Rats; Rats, Sprague-Dawley; Satiation; Splanchnic Nerves; Synaptic Transmission

This study extends a recent observation that Otsuka Long-Evans Tokushima Fatty (OLETF) rats show no expression of the cholecystokinin (CCK)-A receptor gene in the pancreas because of a genetic abnormality. We compared the changes in pancreatic regeneration in terms of wet weight and protein and DNA contents after partial pancreatectomy (30% resection) in OLETF and control (Long-Evans Tokushima Otsuka: LETO) rats and examined whether the CCK-B receptor has a role in pancreatic regeneration after pancreatectomy. The pancreatic wet weight increased significantly with age in both OLETF and LETO rats regardless of surgical procedure, but the increase with respect to time was significantly less in OLETF than in LETO rats. The protein and DNA concentrations in the pancreas (mg/g wet tissue) were comparable for both strains after sham operation. However, they were significantly lower than pancreatectomy in OLETF rats compared to those after sham operation, whereas they were comparable in LETO rats regardless of surgical procedure. The ratio of protein content/DNA content (cell size) was significantly lower in OLETF than LETO rats under all conditions. CCK-B receptor gene expression was not enhanced after pancreatectomy. In conclusion, the CCK-A receptor is not an absolute requirement for pancreatic normal growth but is important for pancreatic regeneration.

Topics: Animals; Blotting, Northern; Body Weight; Cholecystokinin; DNA; Eating; Gene Expression; Male; Organ Size; Pancreas; Pancreatectomy; Protein Precursors; Proteins; Rats; Rats, Inbred Strains; Receptor, Cholecystokinin A; Receptor, Cholecystokinin B; Receptors, Cholecystokinin; Regeneration; RNA, Messenger

Plasma somatostatin and cholecystokinin are two gut peptides with opposite functions which are regulated by two different parts of the autonomic nervous system. Previously we have shown that plasma somatostatin and cholecystokinin levels are higher in preterm infants during the 1st d of life than in adults or in their mothers, and that plasma somatostatin is negatively correlated to gestational age. We have longitudinally studied these two peptides in 28 preterm infants, 17 boys and 11 girls, up until the age of 2 y. The mean (SD) gestational age was 32.3 (2.8) wk, the mean birth weight was 1877 (515) g, and the mean birth length was 42.8 (3.8) cm. Blood samples were taken on the 1st d of life, at 6 wk, and at 3, 6, 12, and 24 mo of age. Plasma was analyzed by specific somatostatin and cholecystokinin RIAs. The median plasma somatostatin and cholecystokinin levels were lowest at 3 mo (somatostatin = 17.4/cholecystokinin = 10.5 pmol/L) and highest at 6 mo (somatostatin = 37.3/cholecystokinin = 27.1 pmol/L). At 24 mo plasma somatostatin remained at the same level, and cholecystokinin had decreased to half that level. After the 1st d of life plasma somatostatin and cholecystokinin levels were not correlated to gestational age or attained weight or length. The plasma somatostatin level at 3 mo of age was negatively correlated to the increment in knee-heel distance between 3 and 6 mo of age.

Topics: Adult; Aging; Body Height; Body Weight; Breast Feeding; Cholecystokinin; Female; Gestational Age; Human Growth Hormone; Humans; Infant Food; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Longitudinal Studies; Male; Respiratory Distress Syndrome, Newborn; Time Factors

Because it is commonly assumed that the major role of visceral afferents in food intake control is to terminate meals by carrying negative-feedback signals to the brain, we hypothesized that overconsumption should occur in rats with chemically lesioned visceral afferents if they were presented with an unfamiliar diet. Adult male Sprague-Dawley (SD) rats were treated with multiple doses of capsaicin or vehicle as a control. Five weeks later, a series of 3-h feeding tests after 24-h deprivation was carried out, first with chow and then with either a solid (vegetable shortening) or liquid (Ensure) unfamiliar high-fat diet. Both groups consumed similar amounts of their powdered chow maintenance diet, but capsaicin-treated rats consumed at least 50% more of either high-fat diet than vehicle controls (P < 0.01) at the beginning of the first trial. During second and third trials with the now-familiar high-fat diet, intake was no longer significantly different between the two groups, suggesting rapid engagement of redundant control mechanisms. These results support a role of capsaicin-sensitive visceral afferents in providing negative feedback for early meal termination during the ingestion of unfamiliar diets.

Topics: Afferent Pathways; Animals; Body Weight; Capsaicin; Cholecystokinin; Conditioning, Psychological; Dietary Fats; Digestive System; Digestive System Physiological Phenomena; Feeding Behavior; Ganglia, Spinal; Male; Nodose Ganglion; Rats; Rats, Sprague-Dawley; Satiation; Thioglycolates; Vagus Nerve

The present study was performed to examine the effect of ageing on pancreatic hyperplasia observed after proximal small bowel resection (PSBR). Young and old Wistar rats were randomly assigned to two groups, which underwent either an approximate 90% PSBR or a jejunal and ileal transection (TRC). One week after the operation, the pancreatic wet weight and the protein, DNA and RNA content of the pancreas were all significantly higher in young PSBR rats than in young TRC rats. However, no differences were seen in the old rat groups. Plasma enteroglucagon levels were elevated in both young and old PSBR rats, but the ratio of increase between the PSBR and TRC groups was significantly higher in young rats. Plasma cholecystokinin and gastrin levels did not increase after PSBR in either the young or old rats. These findings suggest that pancreatic hyperplasia observed after PSBR is attenuated by ageing, probably due to an insufficient increase in plasma enteroglucagon levels.

Topics: Aging; Amylases; Animals; Body Weight; Cholecystokinin; DNA; Eating; Gastrins; Glucagon-Like Peptides; Hyperplasia; Intestine, Small; Lipase; Male; Organ Size; Pancreas; Radioimmunoassay; Rats; Rats, Wistar; RNA; Trypsinogen

We investigated pancreatic enzyme secretion in response to soybean trypsin inhibitor (SBTI) in rats fed amino acids as a nitrogen source, from the fetal stage to adulthood. Pregnant rats were divided into two groups 4 d before parturition. During gestation and nursing, one group was fed a 15% protein diet (protein-fed rats) and the other (amino acid-fed rats) a 15% amino acid mixture diet that simulated the composition of the protein diet. Each male offspring was weaned at 4 wk after parturition and fed the same diet as fed to its dam for an additional 6 wk. Pancreatic amylase secretion in response to an intraduodenal infusion of SBTI (10 mg/rat) was observed in the protein-fed rats but not in the amino acid-fed rats. Amylase secretion in response to an intravenous injection of cholecystokinin (CCK) (10 ng/kg rat) was observed in both groups, and the magnitude of the response was significantly higher in the amino acid-fed rats than in the protein-fed rats. An increase in the level of plasma CCK in response to SBTI was observed in the protein-fed rats but not in the amino acid-fed rats. These results suggest that the long-term amino acid diet, because of its ability to inhibit the SBTI-stimulated CCK-releasing process in the small intestine of rats, reduced the pancreatic enzyme secretion response to a trypsin inhibitor. Six rats fed the amino acid mixture until 1 wk after weaning were fed the protein diet for the next 5 wk. These rats showed no pancreatic amylase secretion in response to SBTI, suggesting that dietary components around the weaning stage may affect the development of the ability of small intestinal cells to recognize a trypsin inhibitor.

Topics: Amino Acids; Amylases; Animals; Body Weight; Cholecystokinin; Dietary Proteins; Egg Proteins; Female; Kidney; Liver; Male; Neurotransmitter Agents; Organ Size; Pancreas; Pregnancy; Rats; Rats, Wistar; Spleen; Time Factors; Trypsin Inhibitors

Chronic feed restriction of prepubertal male lambs adversely affects reproductive development by inhibiting the pulsatile release of luteinizing hormone (LH). Because this effect can be reversed by ad libitum feeding, the associations between diet-induced increases in LH release and concurrent changes in body weight gain, serum glucose. CCK peptide, and CCK mRNA were examined. Neonatally castrated male lambs received a restricted ration to maintain their respective weaning weights beginning at 8 wk of age. At 23 wk of age, lambs were assigned randomly to receive additional feed equivalent to 0%, 50%, or 100% of their previous daily intake. Serum profiles of LH and glucose were determined 2 and 4 wk after onset of the increased intakes. At 27 wk of age, lambs were euthanized and both hypothalamic and cerebral cortical tissues were collected for analysis of CCK peptide and CCK mRNA. With additional intakes, body weight gain increased (P < 0.001) proportional to the graded increases in feed intake. Mean serum LH concentrations, LH peak frequencies, and serum glucose concentrations also increased (P < 0.05) progressively among the 0%, 50%, and 100% dietary intake groups. Neither CCK peptide nor CCK mRNA differed (P > 0.05) among dietary groups suggesting that endogenous CCK in the whole hypothalamus did not change with the feeding-induced increase in LH release. Concentrations of CCK peptide in cerebral cortex were greater (P < 0.05) than hypothalamic concentrations, but there were no differences between hypothalamus and cerebral cortex in the relative abundance of CCK mRNA. In summary, dietary stimulation of growth-retarded male lambs resulted in progressive increases in body weight gain, mean serum LH, serum glucose, and LH peak frequencies. Because hypothalamic levels of CCK peptide and CCK mRNA did not change during feeding-induced secretion of LH, endogenous CCK in the hypothalamus seems unlikely as a chronic mediator of nutrition-sensitive LH release.

Topics: Animals; Blood Glucose; Body Weight; Cerebral Cortex; Cholecystokinin; Diet; Food Deprivation; Gonadotropin-Releasing Hormone; Hypothalamus; Luteinizing Hormone; Male; N-Methylaspartate; Orchiectomy; RNA, Messenger; Sheep

The genetically obese Zucker rat (fa/fa) is hyperphagic compared to lean controls (Fa/?). This hyperphagia is characterized by increased meal size. Cholecystokinin (CCK) has been shown to decrease meal size in many species including humans. In the present study we investigated the role of endogenous CCK in mediating the hyperphagia of male and female obese Zucker rats. CCKA-type receptors were blocked with the specific antagonist, devazepide, and test meal size was measured. Male obese and lean rats significantly increased food intake following devazepide. Neither obese nor lean female rats significantly increased food intake following devazepide. This is the first demonstration of a gender difference in endogenous CCK-mediated satiety. These results have implications for the higher incidence of eating disorders in females.

Topics: Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Eating; Energy Intake; Female; Male; Rats; Rats, Zucker; Receptor, Cholecystokinin A; Receptors, Cholecystokinin; Satiety Response; Sex Factors

It has been proposed, but never demonstrated, that glucose-responsive neurons are essential for the long-term regulation of body weight, and that mice injected with gold-thio-glucose (GTG) become obese due to destruction of glucose-responsive neurons. To assess these hypotheses, mice were injected with either saline (control) or a dose of GTG that produces obesity, and the effects on feeding of peripheral injection of saline, glucose, 2-deoxyglucose (2-DG), or cholecystokinin (CCK) were measured. In control mice, 2-DG increased, whereas glucose and CCK decreased, food intake significantly. In contrast, in GTG-treated mice, 2-DG and glucose did not have a significant effect on food intake. The GTG-treated mice remained sensitive to the inhibitory effect of CCK on food intake. These data indicate that i.p. injection of GTG, which produces obesity, also destroys glucose-responsive neurons, consistent with the hypothesis that glucose-responsive neurons contribute to the long-term regulation of body weight.

Topics: Animals; Aurothioglucose; Body Weight; Cholecystokinin; Deoxyglucose; Drug Resistance; Eating; Glucose; Injections, Intraperitoneal; Male; Mice; Mice, Inbred C57BL; Neurons; Time Factors; Ventromedial Hypothalamic Nucleus

Calcitonin gene-related peptide (CGRP) has been reported to relax, in a concentration-dependent manner, cholecystokinin-induced tension in guinea pig gallbladder strips. It is now shown that this CGRP-induced relaxation is body weight dependent with the degree of relaxation inversely related to weight. Radioimmunoassay demonstrated that the amount of CGRP in the gallbladder increased with body weight. Receptor binding showed that the number of binding sites and the affinity of the receptor decreased with increasing body weight. CGRP may play a role in the normal pattern of gallbladder contraction and relaxation. Decreased motility, even between periods of complete emptying, has been demonstrated to have a role in gallbladder diseases. The decreased sensitivity of the gallbladder to CGRP may explain the increase in abnormalities with age.

Topics: Animals; Body Weight; Calcitonin Gene-Related Peptide; Cholecystokinin; Gallbladder; Guinea Pigs; In Vitro Techniques; Muscle Contraction; Muscle Relaxation

Previous studies have suggested that the metabolism of methyl groups is an important factor in the function of the exocrine pancreas. Ethionine, an inhibitor of cellular methylation reactions, produces hemorrhagic pancreatitis when administered to mice fed a choline-deficient diet. Glycine N-methyltransferase, an enzyme which regulates the ratio of S-adenosylmethionine to S-adenosylhomocysteine, is particularly abundant in the exocrine pancreas. Since de novo synthesis of methyl groups requires the participation of folate coenzymes, we investigated the effect of folate deficiency on pancreatic exocrine function. Rats were fed an amino acid-defined folate-deficient diet or the same diet supplemented with folate ad libitum. A third group received the folate supplemented diet pair-fed to the deficient group. After 3 and 5 wk, pancreatic amylase secretion was measured in perfused duodenal segments of anesthetized animals before and after cholecystokinin injection. Pancreatic secretion was significantly reduced in the deficient group compared with the pair-fed control group after 5 wk. These results indicate that severe folate deficiency impairs pancreatic exocrine function.

Topics: Aging; Amino Acids; Amylases; Animals; Body Weight; Cholecystokinin; Folic Acid Deficiency; Male; Methylation; Pancreas; Rats; Rats, Sprague-Dawley

This study compared the effects of bilateral subdiaphragmatic vagotomy on the Fos-like immunoreactivity (FLI), a marker of neuronal activation, in rat brain induced by two anorectic agents, cholecystokinin (CCK) and the serotonin agonist, dexfenfluramine (DFEN). In the nonvagotomized rats, both CCK (5 micrograms/kg, IP) and DFEN (2 mg/kg, IP) induced FLI in the nucleus of the solitary tract (NST), the external subdivision of the lateral parabrachial nuclei (LPBE), the lateral subdivision of the central amygdaloid nucleus (CeL), and the bed nucleus of the stria terminalis (BST). However, subregional distribution of the FLI induced by the two agents was different in most of these regions. Additionally, the area postrema and the medial subdivision of the hypothalamic paraventricular nucleus were preferentially activated by CCK but not DFEN, while the caudate-putamen was activated by DFEN but not CCK. Bilateral subdiaphragmatic vagotomy completely abolished CCK-induced FLI in all the brain regions but did not attenuate DFEN-induced FLI in any of these regions, including the NST. The results of the present study suggest that DFEN-activation of the NST-LPBE-CeL/BST neuraxis is not mediated by the vagus nerve. On the other hand, and consistent with a variety of other data, activation of various parts of the brain by peripherally administered CCK depends on a vagal pathway. These data are discussed in relation to a previously proposed interaction between CCK and serotonin in mediating satiety.

Topics: Animals; Body Weight; Brain Chemistry; Cholecystokinin; Fenfluramine; Immunohistochemistry; Male; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley; Vagotomy

Insulin acts in the brain to reduce food intake and body weight. Cholecystokinin (CCK) reduces meal size when administered peripherally. The purpose of these experiments was to examine their interaction. In Experiment 1, Long-Evans rats were infused with vehicle or insulin at doses from 0.5 to 2.0 mU/day into the third cerebral ventricles. Doses of 1.0 mU/day and higher caused reduced body weight. A dose of 0.5 mU/day was therefore taken to be subthreshold. In Experiment 2, rats receiving 0.5 mU/day of insulin intracerebroventricularly had greater suppression of 30-min meal size in response to intraperitoneal CCK-8 at doses from 0.25 to 8 mg/kg than did rats receiving intracerebroventricular saline. By itself, the insulin had no effect on body weight or meal size. However, a change of sensitivity to CCK by control rats over the course of the experiment clouded the interpretation. A third experiment was therefore conducted in which rats received an acute intracerebroventricular injection of insulin (0.1 mU) or saline 1 h prior to a 30-min meal, and IP CCK-8 (4 mg/kg) or saline immediately prior to the meal. As in Experiment 2, insulin, itself, had no effect on meal size but enhanced the anorexic effect of CCK. These results are consistent with the hypothesis that central insulin acts by altering sensitivity to satiety agents.

Topics: Animals; Body Weight; Brain; Cholecystokinin; Eating; Energy Intake; Hunger; Insulin; Male; Rats; Satiety Response

The effects of the intraduodenal administration of a low dose of CR-1505 for 3-7 days on the gene expression of cholecystokinin (CCK), plasma CCK concentration, and CCK content in the intestinal mucosa were examined in rats. The simultaneous changes of protein and enzyme content in the pancreas were also determined. CR-1505 was infused continuously into the duodenum at a dose of 3 mg/kg per day, calculated to correspond to a dose of 150-200 mg/day in humans. Seven days after the administration of CR-1505, a liquid meal (4.5 kcal/3 ml) was introduced into the stomach and changes in the intestinal CCK content and plasma CCK concentration were examined. The level of CCK mRNA in the intestine was significantly higher in rats treated with CR-1505 than in control rats. The plasma CCK concentration, the CCK content of the intestinal mucosa, and the composition of pancreatic enzymes did not significantly differ in rats treated with CR-1505 and the untreated controls. In control rats, the administration of the liquid meal increased the plasma CCK concentration and significantly decreased the intestinal CCK content in water extracts, but did not affect the amount extracts in acid whereas the ingestion of the meal did not cause any significant changes in rats treated with CR-1505. These findings indicate that a low dose of CR-1505 stimulates the gene expression of CCK without enhancing CCK release or exerting an effect on the pancreas.

Topics: Animals; Base Sequence; Body Weight; Cholecystokinin; Drug Administration Routes; Gene Expression; Hormone Antagonists; Intestinal Mucosa; Male; Molecular Sequence Data; Pancreas; Proglumide; Radioimmunoassay; Rats; Rats, Sprague-Dawley; RNA, Messenger; Trypsin

Biliopancreatic bypass (BPB), a bariatric surgical procedure, leads to a malnutrition-induced general visceral atrophy except for the pancreas. This work investigates the implication of cholecystokinin (CCK) in the exocrine pancreatic adaptive process using a plasma CCK assay and the CCK receptor antagonist CR 1409. No significant reduction in weight and DNA content of the pancreas was noted 36 days after BPB, while a strong decrease in protein, enzymes and RNA contents indicating cellular hypotrophy became apparent. CR 1409 treatment strongly depressed pancreatic weight and its DNA content in BPB animals, suggesting an additional hypoplasia; however, the reduction in pancreatic enzyme content was not aggravated. BPB increased plasma CCK concentrations by 160%, unrelated to CR 1409 treatment. These results indicate that: (1) CCK is involved in the pancreatic adaptive response after BPB in rats, and (2) in the context of a protein malnutrition state, CCK dissociates its pancreatic growth and enzymatic effects, favouring the former.

Topics: Adaptation, Physiological; Animals; Biliopancreatic Diversion; Body Weight; Cholecystokinin; Data Interpretation, Statistical; DNA; Male; Organ Size; Pancreas; Proglumide; Proteins; Rats; Rats, Wistar; RNA

Peripheral administration of the brain/gut peptide cholecystokinin (CCK) has been demonstrated to inhibit food intake in a variety of species, and administration of the specific type A CCK receptor antagonist devazepide increases food intake in a variety of experimental paradigms. The potency of CCK to inhibit intake depends upon a variety of factors, but CCK is generally less potent under conditions of elevated food intake. At different developmental stages, rats' intake requirements differ as growth rates change. To determine whether CCK plays a variable role in the control of intake in rats of different ages, we examined the feeding-inhibitory effect of various doses of CCK and the feeding-enhancing potential of various doses of devazepide on glucose consumption (0.5 kcal/ml) in male and female rats at 45-70 and 110-130 days of age. CCK was more potent in older male and female rats than in younger rats, and inhibited intake in a dose-related fashion. In younger rats, the efficacy of CCK was attenuated and the inhibition was not dose related. Administration of devazepide had no effect on intake in younger rats of either sex, but significantly increased glucose consumption in the older rats. These data suggest that during a period of rapid growth and high levels of food intake relative to body weight, adolescent rats are relatively insensitive to exogenous CCK and endogenous CCK does not appear to play a significant role in controlling their intake.

Topics: Age Factors; Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Eating; Energy Intake; Female; Male; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Satiety Response; Sex Factors

The effect of long term administration of a synthetic cholecystokinin (CCK) receptor antagonist CR1505 (loxiglumide) on pancreatitis was examined in rats after pancreatic duct ligation (PL) with an internal bile fistula. All rats were given both 6 mg/day of CR1505 continuously infused intraduodenally with an osmotic pump and 32 mg/day introduced into the stomach with an orogastric tube. Rats were killed 7, 14, and 28 days after PL, and changes of body weight, pancreatic wet weight, daily food intake, pancreatic protein content, and histology, plasma amylase concentration, and both plasma and duodenal CCK concentrations were examined. Administration of CR1505 for 7 days from immediately after PL, resulted in decrease of body weight, increase of daily food intake, and significant increases of intestinal CCK concentration and the level of CCK mRNA. However, its administration from day 7 to day 14 or 28 did not improve any of the parameters examined except inflammatory infiltration of the pancreas on the 14th postoperative day. These results suggest that CR1505 may have a beneficial effect on recovery from pancreatitis when administered during the early stage, but not when administered during a later stage.

Topics: Animals; Body Weight; Cholecystokinin; Duodenum; Eating; Intestinal Mucosa; Ligation; Male; Organ Size; Pancreatic Ducts; Pancreatitis; Proglumide; Proteins; Rats; Rats, Wistar; Receptors, Cholecystokinin; Regeneration

Meal patterns were recorded for 10.5 h in six lean and eight obese adult male Zucker rats after treatment with the cholecystokinin type A (CCKA) receptor antagonist, devazepide (750 micrograms/kg, IP, at 1330 h) or vehicle. In lean rats, devazepide significantly increased total food intake by 11%, average meal size by 35%, and meal duration by 49%. Devazepide also significantly decreased the average number of meals by 18%, although this was a smaller effect. Devazepide had none of these effects in obese rats. Devazepide treatment altered the meal pattern of lean rats so that it was similar to that of obese rats. These results demonstrate that endogenous CCK has a satiating effect in lean, but not in obese, male Zucker rats, which is the first demonstration of a loss of a physiological satiety signal in the obese Zucker rat. This defect could be due to: 1) a decrease in the release of endogenous CCK, 2) a decrease in the rate of CCK synthesis, or 3) the production of an abnormal form of CCK.

Topics: Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Feeding Behavior; Male; Rats; Rats, Zucker; Receptors, Cholecystokinin; Satiety Response

The purpose of the study was to evaluate the trophic effects of endogenous hypergastrinemia and hypercholecystokininemia on intact and regenerating rat liver. We also examined the effects on the liver of portacaval shunting (PCS) alone or together with hypergastrinemia or hyperCCKemia. PCS is known to enhance the trophic effects of gastrin on the so-called enterochromaffin-like cells of the stomach and of CCK on the pancreas.. Hypergastrinemia was induced by treatment with omeprazole (400 mumol/kg/day) or extirpation of the acid-producing part of the stomach (fundectomy). HyperCCKemia was induced by pancreaticobiliary diversion (PBD). After 4 weeks half of the rats were killed; the rest underwent partial hepatectomy and were killed 60 h later. PCS rats were killed 4 weeks after start of omeprazole treatment or after PBD. The concentrations of circulating gastrin and CCK were measured by radioimmunoassay. The liver weight and DNA content were analyzed.. Endogenous hypergastrinemia and hyperCCKemia failed to stimulate growth of either intact or regenerating liver. There were no differences in liver weight and DNA content between rats subjected to PCS and to combinations of PCS and omeprazole treatment, on the one hand, and PCS and PBD, on the other.. Gastrin and CCK are unlikely to be physiologically important in the regulation of liver growth and regeneration in the rat.

Topics: Animals; Biliopancreatic Diversion; Body Weight; Cholecystokinin; DNA; Gastric Fundus; Gastrins; Liver; Liver Regeneration; Male; Omeprazole; Organ Size; Portacaval Shunt, Surgical; Rats; Rats, Sprague-Dawley

In this animal study we investigated the absorption of free fatty acids and triglycerides after gastrectomy. The levels of the hormones cholecystokinin and secretin were measured in response to a controlled enteral fat load (Lipofundin 20% MCT emulsion). We studied fat absorption in three groups of animals: the gastrectomy group in which lipid emulsion was administered in the duodenum, and two groups of controls that received the same infusion in the duodenum or stomach, respectively. Infusing the fat load directly into the duodenum, rather than the stomach, resulted in delayed absorption of fatty acids. In the gastrectomized animals there was, in addition, increased absorption of triglycerides. Medium- and long-chain fatty acids were found to be an adequate stimulus for secretion of the gastrointestinal hormones cholecystokinin (CCK) and secretin. In the gastrectomized group, higher baseline levels of both CCK and secretin were observed. CCK showed no response to the lipid stimulus, whereas a secretin response was observed over and above the raised baseline level. The gastrectomized animals showed a markedly restricted growth rate, as measured by body weight; however, they continued to gain weight in a linear fashion up to the end of the study period. No alterations in morphology of CCK-secreting cells were found.

Topics: Animals; Body Weight; Cholecystokinin; Dietary Fats; Drug Combinations; Fat Emulsions, Intravenous; Fatty Acids, Nonesterified; Gastrectomy; Intestinal Absorption; Male; Phospholipids; Postgastrectomy Syndromes; Rats; Rats, Sprague-Dawley; Secretin; Sorbitol; Triglycerides

The effect of a fat and protein rich test meal of 800 kcal on subjective satiety ratings and on plasma cholecystokinin (CCK) 8-S was studied in 18 acutely ill patients with anorexia nervosa, 11 former anorectic patients, who were weight recovered for at least 4 years, and in 25 healthy young women. Eleven normal weight patients with bulimia nervosa were studied in the same experiment. Satiety ratings were significantly elevated in acutely ill anorectic and bulimic patients. CCK 8-S values were significantly stimulated by the test meal in all groups except from the bulimic group. Anorectic patients and weight recovered anorectics had normal values before and after the test meal. Bulimic patients had significantly lower values. These data suggest that CCK 8-S is not involved in the regulation of short-term satiety in anorexia and bulimia nervosa.

Topics: Adult; Anorexia Nervosa; Body Weight; Bulimia; Cholecystokinin; Energy Intake; Female; Humans; Satiety Response

Topics: Anastomosis, Roux-en-Y; Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Dose-Response Relationship, Drug; Fasting; Feeding Behavior; Gastrectomy; Phenylurea Compounds; Rats; Receptors, Cholecystokinin; Sincalide; Time Factors

Concentrations of cholecystokinin (CCK) and secretin from neonatal guinea pig plasma were evaluated in relation to pancreatic growth, and secretion from dispersed pancreatic acini. Plasma CCK was low at birth (3.1 +/- 0.8 pmol/L) but rose markedly by day 15 (11.0 +/- 0.8 pmol/L, p < 0.001). Plasma secretin was also low at birth (3.8 +/- 0.8 pmol/L) but peaked on day 4 (17.0 +/- 1.4 pmol/L, p < 0.001) and remained elevated through d 15. Adult nonfasting plasma CCK and secretin levels were 12.3 +/- 0.8 and 8.9 +/- 1.5 pmol/L, respectively. Pancreatic weight more than doubled during the first week of life, with the greatest increase during the first 4 d (156 +/- 4 to 262 +/- 10 mg/100g body wt, p < 0.001). Body weight increased most dramatically during the second week (126 +/- 9 to 190 +/- 7 g p < 0.001). Amylase secretion from isolated acini stimulated by CCK-8, carbachol, phorbol ester, forskolin, and calcium ionophore (A23187) was present at birth. The percentage of total amylase content secreted in response to CCK, carbamylcholine, and secretin did not change during the first 2 wk of neonatal life, and was independent of surges in circulating CCK and secretin. These results indicate that functional maturity of the guinea pig pancreas for amylase secretion occurs early and is different from the rat, mouse, pig, and human. Since results can readily be compared between animals of different postnatal ages, the neonatal guinea pig is ideally suited for the study of hormonal effects on acinar cell function.

Topics: Amylases; Animals; Animals, Newborn; Body Weight; Carbachol; Cholecystokinin; Cyclic AMP; Guinea Pigs; Nucleic Acids; Organ Size; Pancreas; Secretin; Tetradecanoylphorbol Acetate

The pancreas has been reported as a possible target for FK506 toxicity. This study was conducted to examine the effects of FK506 on the structure and function of pancreatic acinar cells.. Male Sprague-Dawley rats received an intramuscular injection of saline or FK506, and pancreatic acini were isolated on the day of sacrifice.. FK506 caused a time-dependent suppression in amylase secretory response to cholecystokinin or carbachol at days 3-14, and increases in amylase and trypsinogen content at days 7-14. The properties of cholecystokinin and scopolamine binding sites in acini were not altered by FK506. Amylase release by A23187 and secretin were decreased by FK506, but those by phorbol ester 12-O-tetradecanoylphorbol-13-acetate, forskolin, 5'-cyclic adenosine monophosphate and vasoactive intestinal peptide were not changed. Increases in cytosolic free calcium concentration induced by cholecystokinin were not changed by FK506. Histologically, a significant increase in cytoplasmic zymogen granules was observed in pancreas from FK506-treated rats.. These data suggest that FK506 induced changes in function and metabolism in pancreatic acinar cells, and these changes might be caused by altering postreceptor loci in stimulus-secretion coupling.

Topics: Amylases; Analysis of Variance; Animals; Atropine; Body Weight; Calcimycin; Calcium; Carbachol; Cholecystokinin; Colforsin; Cytosol; Dose-Response Relationship, Drug; Feeding Behavior; Kinetics; Male; N-Methylscopolamine; Pancreas; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Reference Values; Scopolamine; Scopolamine Derivatives; Secretin; Sincalide; Tacrolimus; Tetradecanoylphorbol Acetate; Time Factors; Trypsinogen; Vasoactive Intestinal Peptide

This study was conducted in rats to investigate the influence of exogenously administered estradiol (ESD) and/or cholecystokinin (CCK) on components and secretions of the pancreatic acini. Intact male rats were treated for 14 d with exogenous administration of ESD, CCK, or ESD+CCK. After 14 d CCK treatment induced significant increases in DNA and RNA contents, and DNA/RNA ratio in the pancreas, indicating hyperplasia and hypertrophy of the pancreas, however, ESD treatment did not have these effects. Both ESD treatment and CCK treatment induced significant increases in amylase and trypsinogen contents in pancreatic acini and each decreased secretion from acini in response to CCK. Combined treatment with ESD plus CCK augmented these effects on enzyme contents and secretion. The results indicate that exogenous administration of CCK has trophic effects on the exocrine pancreas, increasing effects on enzyme contents and inhibitory effects on amylase secretion. In contrast, exogenous administration of ESD had no trophic effects on pancreas, but had increasing effects on enzyme contents and inhibitory effects on amylase secretion. The results suggest that the effects of exogenous ESD and CCK on pancreas are not similar to each other, but both ESD and CCK may be involved in regulating pancreatic exocrine functions.

Topics: Amylases; Animals; Body Weight; Cholecystokinin; Estradiol; In Vitro Techniques; Male; Pancreas; Rats; Rats, Sprague-Dawley; Reference Values

The ability of nanomolar concentrations of guanine, but not adenine, nucleotides to inhibit specific 125I-Bolton-Hunter CCK binding to ligated rat vagus nerve demonstrated that vagal CCK binding sites were linked to G-proteins during axonal transport. The GTP analogue, GTP[S], reduced specific binding to both anterogradely and retrogradely transported binding sites by more than 90% at 1 microM. Transport of these putative receptor-G-protein complexes was examined under conditions of food deprivation or physiological hyperphagia induced by either lactation or genetic obesity. None of the physiological or imposed manipulations of food intake had any effect on the axonal transport of CCK binding sites. Transection of the cervical vagus resulted in an accumulation of binding sites at the lesion site that was indistinguishable from that seen following ligation for the same period.

Topics: Animals; Axonal Transport; Body Weight; Cholecystokinin; Eating; Female; Food Deprivation; GTP-Binding Proteins; Lactation; Male; Rats; Rats, Zucker; Receptors, Cholecystokinin; Satiety Response; Vagus Nerve

The effect of gastric fundectomy with hypergastrinaemia on the pancreas in rats was studied for 14 months. Rats with hypercholecystokininaemia that had had a pancreaticobiliary diversion (PBD) operation and sham operated rats served as controls. Fundectomised rats showed a significant increase in pancreatic weight and total DNA and protein content compared with sham operated rats. DNA flow cytometry showed a significantly higher ratio of tetraploid to diploid nuclei in pancreatic tissue after fundectomy than after sham operation. Mean values of all these variables were significantly lower after fundectomy than after PBD. Acidophilic atypical acinar cell foci of the pancreas were diagnosed in both fundectomised and PBD operated rats, but not in sham operated controls. The volume density and 3H-thymidine labelling index of the acidophilic atypical acinar cell foci were significantly lower after fundectomy than after PBD. Changes consistent with pancreatic adenoma were diagnosed in the PBD group only. In conclusion, fundectomy lasting about half of the life span in rats causes pancreatic hyperplasia and hypertrophy, as well as development of acidophilic atypical acinar cell foci. Although hypergastrinaemia is a prominent feature, it may not be the only factor responsible for this pancreaticotrophical effect of fundectomy.

Topics: Animals; Autoradiography; Body Weight; Cholecystokinin; DNA; Gastric Fundus; Gastrins; Hypertrophy; Male; Organ Size; Pancreas; Ploidies; Rats; Rats, Wistar; Time Factors

The role of cholecystokinin (CCK) has been explored in pancreatic carcinogenesis following pancreatobiliary diversion (PBD), using the specific CCK receptor antagonist CR-1409. Male Wistar rats (n = 80) weighing 70-100 g were given weekly i.p. injections of azaserine (30 mg kg-1 week-1) for 3 consecutive weeks. One week later animals were randomised to receive either PBD or sham PBD and thereafter to receive s.c. injections of either saline or CR-1409 (10 mg kg-1 day-1, 5 days a week). Six months after operation surviving rats were killed as follows: sham + saline 20, PBD + saline 19, sham + CR-1409 14, PBD + CR-1409 11. Cardiac blood was taken for CCK assay and the pancreas was excised for wet weight measurement and quantitative estimation of atypical acinar cell foci (AACF), the precursor of carcinoma. PBD reduced median body weight (3-20% less than shams) but trebled the absolute and relative pancreatic weights (P < 0.001). CR-1409 blunted this adaptive response to PBD, reducing absolute pancreatic weight by 35% (P < 0.005). PBD quadrupled circulating CCK concentrations, regardless of the antagonist treatment. Acidophilic AACF occurred only in rats with PBD. CR-1409 markedly reduced the number of observed acidophilic AACF by 90% (P < 0.001) and the number of foci per pancreas by 93% (P < 0.001). Moreover, CR-1409 reduced the mean focal diameter of each lesion by 18% (P < 0.005), the mean focal volume by 58% (P < 0.05) and the percentage of pancreas occupied by acidophilic foci by 95% (P < 0.001). PBD enhances pancreatic carcinogenesis by causing hypercholecystokininaemia, and CR-1409 largely inhibits this enhancement.

Topics: Animals; Azaserine; Biliopancreatic Diversion; Body Weight; Cholecystokinin; Cocarcinogenesis; Male; Organ Size; Pancreas; Pancreatic Neoplasms; Precancerous Conditions; Proglumide; Rats; Rats, Wistar

There is considerable evidence that the gastrointestinal hormone cholecystokinin (CCK) induces satiety and reduces food intake in both animals and humans. Impaired CCK secretion was recently reported in patients with bulimia nervosa (BN) in whom plasma CCK responses to a standardized mixed-liquid meal were significantly lower than in controls. The present study was undertaken to determine whether CCK levels were abnormal in another relatively common eating disorder, anorexia nervosa (AN), before and after therapy and to investigate the relationship to the abnormal eating behavior. Plasma CCK, serum glucose, and immunoreactive insulin (IRI) responses to a 50-g oral glucose load were measured in 13 women with AN and in nine normal sex- and age-matched controls. The AN patients were all hospitalized during treatment; following partial restoration of body weight, the tests were repeated. Initial body weights were 70.8% +/- 1.8% (mean +/- SEM) of ideal body weight (IBW), and following partial restoration were 84.3% +/- 1.4%. Body weights in normal controls were 96.3% +/- 2.1% of IBW. Initial basal CCK concentrations in the AN patients before nutritional and cognitive behavioral therapy were significantly greater than those in controls (P < .01). After partial restoration of body weight, basal CCK concentration in AN patients approached that of control subjects. When AN patients were given a glucose load before therapy, the change in CCK response was diminished when compared with that of controls. However, CCK responses to the glucose load in AN patients following therapy were similar to those of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adult; Anorexia Nervosa; Blood Glucose; Body Weight; Cholecystokinin; Female; Glucose Tolerance Test; Humans; Insulin; Osmolar Concentration; Reference Values

A subacute oral toxicity study of 6-amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187), a new protease-inhibiting agent, was carried out in beagle dogs of both sexes. FUT-187 was administered to dogs at daily oral doses of 15, 50 and 150 mg/kg. Dogs in 150 mg/kg group were given twice a day in a.m. and p.m.. The results were as follows: 1. Changes of physical sign attributed to FUT-187, consisted of vomiting, diarrhea, salivation, decrease of locomotor activity, sedation and hyperemia of eye mucosa. These changes expect vomiting vanished within about 2 hours after treatment. One male given 150 mg/kg died on day 19 and two females given 150 mg/kg were sacrificed on day 55 and 67 due to deterioration of systemic conditions. 2. Body weight gain was suppressed in males given 150 mg/kg and females given 50 mg/kg or more. 3. In hematological examinations, some changes suggesting anemia or inflammation were observed in a few animals received 50 mg/kg or more 4. In serum biochemical examinations, dogs given 50 mg/kg or more had decrease of albumin, total protein, A/G ratio and total cholesterol, increase of GPT activity. In liver function test, decrease of function was observed in a few animals in 150 mg/kg group. These changes diminished by the end of recovery period. 5. In autopsy findings, ulcer formation and desquamation of mucosa in the digestive tract were observed in dead or sacrificed animals and survived animals given more than 50 mg/kg. In sacrificed animals, liver was yellow in color and intussusception was seen. 6. Plasma levels of intact FUT-187 and metabolites on the day 37 or 83 were higher than that on the first day of administration. 7. In histopathological examinations, ulcer formation, desquamation, degeneration and/or atrophy of mucosa in the digestive tract were observed in the animals from 50 mg/kg and 150 mg/kg groups. In addition, fatty deposition in hepatocytes was observed in one dead animal and two sacrificed animals.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Administration, Oral; Animals; Body Weight; Cholecystokinin; Dogs; Drug Administration Schedule; Eating; Electrocardiography; Female; Hematologic Tests; Imidazoles; Kidney Function Tests; Liver Function Tests; Male; Organ Size; Time Factors; Urinalysis

The role of exogenous and endogenous cholecystokinin has been studied in the process of pancreatic regeneration after acute pancreatitis. A mild form of pancreatitis was induced in rats by subcutaneous cerulein at 12 micrograms.kg-1, three times a day for 2 days. After 3 days of rest, the cerulein-treated rats were divided into four groups: rats with acute pancreatitis fed 20% casein, who received no treatment; rats fed 50% casein; rats fed 20% casein supplemented with 1% soybean trypsin inhibitor (SBTI); and rats fed 20% casein who received 1 microgram.kg-1 of subcutaneous cerulein, three times a day. Controls were fed 20% casein plus saline subcutaneously. Rats were killed after 5, 10, or 20 days of treatment. Pancreatitis resulted in significant decreases in pancreatic weight and contents of protein, amylase, chymotrypsin, RNA and DNA. During the regenerative process, 1 microgram.kg-1 of cerulein increased all parameters to control values within 5 days and induced pancreatic growth thereafter. SBTI restored the pancreas to normal after 10 days with cellular hypertrophy; the 50% casein diet gave a response similar to SBTI without hypertrophy. It can be concluded that cerulein and SBTI can accelerate pancreatic regeneration after an attack of acute pancreatitis.

Topics: Acute Disease; Amylases; Animals; Body Weight; Ceruletide; Cholecystokinin; Chymotrypsin; Drug Therapy, Combination; Glycine max; Hypertrophy; Male; Nucleic Acids; Organ Size; Pancreas; Pancreatitis; Proteins; Rats; Rats, Inbred Strains; Regeneration; Trypsin Inhibitors

The role of cholecystokinin (CCK) in induction and maintenance of pancreatic growth stimulated by a high-protein diet was investigated. Rats adapted to 5% casein diet were switched to 70% casein for 21 days. MK-329, a CCK receptor antagonist, was administered at 2.5 mg.kg-1.day-1 ip, beginning on day zero (day zero treatment) or day 7 (midcourse treatment) of feeding 70% casein and thereafter. Another group was returned to 5% casein after 7 days of feeding 70% casein. Feeding 70% casein significantly stimulated increases of 32, 87, 74, 216, and 1,450% in pancreatic DNA, RNA, wet weight, protein content, and chymotrypsin content, respectively. Midcourse treatment with MK-329 was more effective than day zero treatment, and it completely reversed increases in pancreatic weight and RNA content, partially reversed increases in protein and chymotrypsin content, and had no effect on DNA content. Return to 5% casein rapidly reversed increases in pancreatic parameters, except for DNA. The results indicate that CCK is essential for induction and maintenance of dietary protein-stimulated pancreatic hypertrophy.

Topics: Amylases; Animals; Body Weight; Cholecystokinin; Chymotrypsin; Dietary Proteins; DNA; Eating; Male; Organ Size; Pancreas; Proteins; Rats; Rats, Inbred Strains; RNA

This study was undertaken to clarify the role of endogenous cholecystokinin (CCK) in induction of pancreatic growth stimulated by a high protein diet. Rats with i.v. jugular cannulae in place and kept in Bollman cages were adapted to 5% casein diet for 9 days and switched to 70% casein for 2 days. MK-329, a CCK receptor antagonist, and SMS 201-995, a somatostatin agonist, were continuously infused at 0.5 mg/kg/h and 5 micrograms/kg/h, respectively, starting at the onset of feeding 70% casein. The 5 and 70% casein control groups were infused with saline. Feeding 70% casein significantly stimulated pancreatic hyperplasia and tissue hypertrophy. MK-329 and SMS 201-995 totally prevented 70% casein-induced increases in pancreatic weight and total RNA and DNA contents. The results indicate that endogenous CCK is the major factor responsible for pancreatic growth induced by a high protein diet.

Topics: Amylases; Animals; Benzodiazepinones; Body Weight; Caseins; Cholecystokinin; Chymotrypsinogen; Devazepide; Dietary Proteins; DNA; Hyperplasia; Octreotide; Organ Size; Pancreas; Proteins; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; RNA

To ascertain whether the increase in cholecystokinin (CCK) level associated with pancreaticobiliary diversion has a cytoproliferative effect on the liver similar to that on the pancreas, we studied three groups of rats: group I (n = 19) had a pancreaticobiliary diversion and 4 weeks later a 70% liver resection, group II (n = 13) had a liver resection only, and group III (n = 6) underwent a sham liver operation. Tissue samples were taken from the liver and pancreas 48 h after the liver operation. Liver regeneration was evaluated on the basis of continuous incorporation of tritiated thymidine into hepatocytes, liver weight, and DNA content. For confirmation of the increase in CCK levels the effects on the pancreas was studied by measuring wet weight, total protein, and total DNA content. The results showed trophic effects on the pancreas, as expected, but no effects whatsoever on liver regeneration. CCK does not seem to have any role in the regulation of liver regeneration.

Topics: Animals; Biliopancreatic Diversion; Body Weight; Cholecystokinin; Liver; Liver Regeneration; Male; Pancreas; Rats; Rats, Inbred Strains

We conducted a study to examine the role of cholecystokinin in feeding behavior and weight change in rats with obstructive jaundice. Daily food and water intake, body weight, and short-term food intake were determined in two groups of rats with surgically induced obstructive jaundice and in control rats. One group of rats with obstructive jaundice was given L-364,718, a selective cholecystokinin receptor antagonist. Plasma bilirubin and cholecystokinin levels were measured in each rat before and 7 days after surgery. Daily food intake and body weight were decreased in obstructive jaundice rats compared with control rats during the first week after surgery (P less than .05); however, obstructive jaundice rats treated with L-364,718 had increased food intake and body weight (P less than .05). Short-term food intake measured for 30 minutes and 120 minutes in food-deprived obstructive jaundice rats was decreased when compared with control rats (P less than .05), but the obstructive jaundice rats given L-364,718 had increased short-term food intake (P less than .05). Water intake was similar between the two groups of rats. Plasma levels of cholecystokinin and bilirubin were increased in obstructive jaundice rats with and without L-364,718 treatment (P less than .05). The results support the concept that endogenously elevated levels of plasma cholecystokinin play an important role in decreased food intake and subsequent loss of body weight in rats with obstructive jaundice.

Topics: Animals; Benzodiazepinones; Bilirubin; Body Weight; Cholecystokinin; Cholestasis; Devazepide; Feeding Behavior; Male; Rats; Rats, Inbred Strains

Six patients with anorexia nervosa, the same patients after weight normalization, and six healthy control subjects had similar fasting and postprandial plasma cholecystokinin concentrations. These data do not support the hypothesis that low levels of hunger and food intake in anorexic patients reflect hypersecretion of this endogenous hormone, which is thought to inhibit hunger, promote satiety, and reduce feeding.

Topics: Adult; Anorexia Nervosa; Appetite Regulation; Blood Glucose; Body Weight; Cholecystokinin; Eating; Female; Humans; Hunger; Satiation

We studied the behavioral effects of a novel cholecystokinin tetrapeptide (CCK-4) analogue, A71623, with full agonist activity and high affinity and selectivity for the CCK-A receptor subtype relative to the CCK-B receptor. In tests for anorectic activity, A71623 was found to suppress 60-min intakes of a liquid diet in both deprived and sated rats, and the effects were blocked by a selective CCK-A antagonist, A70104. Compared with CCK-8, A71623 was found to have improved potency and duration of action; the most potent route of administration was intraperitoneal. A71623 also suppressed the intake of a liquid diet and a 0.2 M sucrose solution in lean and obese Zucker rats. In daily injection studies, the anorectic activity of CCK-8 diminished rapidly, whereas the suppressant effects of A71623 on food intakes and body weight gains persisted throughout the 11-day treatment period. Finally, A71623 reduced the spontaneous locomotor activity of rats at doses above those required to suppress intakes. These studies are the first to describe the behavioral effects of a potent and highly selective CCK-A receptor agonist.

Topics: Animals; Anorexia; Behavior, Animal; Body Weight; Cholecystokinin; Circadian Rhythm; Eating; Food Deprivation; Male; Motor Activity; Peptides; Rats; Rats, Inbred Strains; Sincalide; Tetragastrin; Time Factors

The role of cholecystokinin in dietary fat-promoted pancreatic carcinogenesis was investigated in azaserine-treated rats, using lorglumide, a highly specific cholecystokinin-receptor antagonist. The animals were killed 8 months after the start of treatment. Cholecystokinin, but not dietary unsaturated fat, increased pancreatic weight. Rats treated with cholecystokinin developed more acidophilic atypical acinar cell nodules, adenomas and adenocarcinomas than control animals. Rats maintained on the high-fat diet developed significantly more adenomas and adenocarcinomas than controls given a diet low in unsaturated fat. Lorglumide largely inhibited the enhancing effect of cholecystokinin, but not of dietary fat, on pancreatic carcinogenesis indicating that it is unlikely that the promoting effect of dietary unsaturated fat on pancreatic carcinogenesis is mediated via cholecystokinin.

Topics: Animals; Azaserine; Body Weight; Cholecystokinin; Dietary Fats; Liver; Male; Organ Size; Pancreas; Pancreatic Neoplasms; Proglumide; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin

The changes in plasma and duodenal cholecystokinin (CCK) concentrations after pancreatic duct occlusion were examined in rats. The rats were sacrificed 1, 3, 7, 10, 14, and 30 days after occlusion of the duct. Histological examination showed acute inflammation on days 1 and 3 after duct occlusion, interstitial fibrosis and regenerative changes on days 7, 10, and 14, and pancreatic atrophy on day 30. The plasma CCK concentration increased from 0.45 pM to 2.0 pM after the occlusion and then remained high throughout the observation period. In contrast to the stable increase in plasma CCK concentration, the CCK content in the duodenum increased on days 1 and 3, decreased on day 7, increased on day 10, reaching over the control level on day 14, and then returned to the control level on day 30. Administration of boiled and 10-fold concentrated rat pancreatic juice or human pancreatic secretory trypsin inhibitor for seven days after pancreatic duct occlusion reversed the decrease in duodenal CCK content. The major molecular forms of duodenal CCK were CCK-8, -33, and -58. These results indicate that (1) basal plasma CCK concentration did not reflect the duodenal CCK content, (2) duodenal CCK content was well correlated with a decrease in inflammation in the pancreas, and (3) a nonenzymatic component in the pancreatic juice reversed the decrease in duodenal CCK content and body weight caused by pancreatic duct occlusion.

Topics: Acute Disease; Animals; Body Weight; Cholecystokinin; Duodenum; Female; Intestinal Mucosa; Ligation; Male; Organ Size; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Inbred Strains; Trypsin

Dietary stimulation has trophic effects on the gastrointestinal tract, whereas prolonged fasting causes mucosal atrophy. Whether gastrointestinal endocrine cells within the mucosa are similarly affected is unknown. The present study was designed to determine the effects of food deprivation and refeeding on cholecystokinin (CCK) and somatostatin in the rat small intestine. RNA was prepared from the duodenum, and peptide and messenger RNA (mRNA) levels of CCK, somatostatin, and beta-actin were analyzed by hybridization with complementary DNA probes. During food deprivation for up to 5 days, plasma CCK levels decreased rapidly, followed by a decline in duodenal CCK mRNA levels and a more gradual decrease in mucosal CCK peptide concentrations. After 3 days of fasting, one group of rats was refed. After only 1 day of refeeding, all parameters (levels of plasma CCK, duodenal CCK mRNA, and duodenal CCK peptide) were restored to control levels. The reduction in CCK mRNA levels seen with fasting was specific, because food deprivation and refeeding produced no changes in either duodenal somatostatin concentrations or mRNA levels of somatostatin and beta-actin. These findings provide initial evidence that food deprivation inhibits duodenal CCK mRNA levels but does not affect duodenal somatostatin.

Topics: Actins; Analysis of Variance; Animals; Body Weight; Cholecystokinin; Duodenum; Food Deprivation; Intestinal Mucosa; Male; Organ Size; Rats; Rats, Inbred Strains; RNA, Messenger; Somatostatin

The effects of the removal of bile from the proximal intestine on pancreas, plasma cholecystokinin (CCK) concentration, and duodenal content of CCK were examined in rats. Bile was excluded from the duodenum and introduced into the distal ileum through a silastic cannula for 7 days. Pancreatic juice was maintained to be normally secreted into the duodenum. After 7-day bile diversion, plasma CCK concentration and duodenal CCK content were significantly increased in bile-diverted rats. Trypsin content in the proximal intestine in bile-diverted rats was one-half that in control. Pancreatic wet weight, protein content, and DNA content in the pancreas were slightly increased, and lipase content was slightly decreased, by bile diversion, but none of these changes was statistically significant. Amylase content significantly decreased and chymotrypsin content significantly increased in bile-diverted rats. Intragastric administration of camostate (trypsin inhibitor) significantly increased plasma CCK concentration in both bile-diverted and control rats, and the net increase was much greater in bile-diverted rats than in control rats. In conclusion, bile diversion increased duodenal CCK content and increased the CCK response to luminal stimulant.

Topics: Amylases; Animals; Bile; Body Weight; Cholecystokinin; Chromatography, Gel; Duodenum; Female; Male; Organ Size; Pancreas; Rats; Rats, Inbred Strains

The authors investigated whether lorglumide a specific CCK-receptor antagonist affects the pancreatic actions of caerulein in female newborn Wistar rats. Pancreatic secretory response (expressed as the decrease in specific trypsin activity in the pancreas) was studied in 11-day-old rats following acute administration of saline (control), caerulein (0.3, 1, or 3 micrograms/kg s.c.) either without or with lorglumide (10 mg/kg s.c.). Lorglumide was given 15 min before caerulein. In chronic studies rats were treated 3x/day for 10 days from the day of birth (Day 1) with caerulein and lorglumide as above. On Day 11 the rats were decapitated and exsanguinated, their pancreas removed and analyzed. Acute administration of caerulein induced a dose-dependent depletion of specific trypsin activity from the pancreas and this was antagonized by lorglumide. Chronic treatment with each dose of the peptide increased total pancreatic trypsin content. Besides, the 3 micrograms/kg dose caused to increase pancreatic protein, DNA, and amylase content and to increase plasma corticosterone level. Chronic administration of lorglumide did not influence normal pancreatic growth, while it strongly inhibited the increase in trypsin content evoked by caerulein. However, lorglumide, given alone or in combination with caerulein, induced a significant increase in pancreatic amylase content without affecting plasma corticosterone level.

Topics: Amylases; Animals; Animals, Newborn; Body Weight; Ceruletide; Cholecystokinin; Corticosterone; Female; Organ Size; Pancreas; Proglumide; Proteins; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; Trypsin

Age related differential gene expression occurs in the neuro-enteral axis. Brain and gut organ weight, total RNA, total protein and three peptides were quantified in 4-, 10- and 37-week-old Sprague-Dawley rats. As animals aged, total RNA decreased in the brain (0.65 +/- 0.3-0.28 +/- 0.03 mg/g), but remained stable in the gut (2.6 +/- 0.3-2.9 +/- 0.4 mg/g). Total protein concentration rose in the duodenum (612 +/- 28-734 +/- 34 mg/g), while levels remained stable in the brain (641 +/- 54-666 +/- 34 mg/g). Three peptides were studied, cholecystokinin (CCK), VIP and secretin. With increasing age, significant changes were found only in CCK a true neural-enteral peptide. The concentration of smaller molecular forms of CCK decreased in the brain (248 +/- 18-188 +/- 21 pmol/g), while they remained stable in the duodenum (33 +/- 2-36 +/- 3 pmol/g). By contrast, the concentration of the larger forms of CCK were stable in the brain (36 +/- 3-40 +/- 4 pmol/g), but rose in the gut (89 +/- 14-134 +/- 17 pmol/g). These data indicate that as rats age there is preprogrammed differential control of gene expression between brain and intestine.

Topics: Aging; Animals; Body Weight; Brain; Cholecystokinin; Digestive System; Gene Expression Regulation; Male; Organ Size; Proteins; Rats; Rats, Inbred Strains; RNA

This study was undertaken to evaluate the effects of Sandostatin, a potent somatostatin analogue, on pancreatic and intestinal growth and plasma and pancreatic levels of insulin-like growth factor I, a known growth factor. Rats weighing 320-330 g, equipped with an intravenous cannula were infused with either bovine serum albumin or Sandostatin at a dose of 5 micrograms kg-1 h-1 for 7 days. Sandostatin caused significant reductions in pancreatic and intestinal weights accompanied by decreases in total DNA, RNA in both organs and total protein in the intestine while total pancreatic enzymes were increased. Plasma cholecystokinin and insulin-like growth factor I were reduced whereas total insulin-like growth factor I pancreatic content was increased. It is suggested that Sandostatin may reduce growth of these two organs by decreasing cholecystokinin and insulin-like growth factor release and their specific effects at the pancreatic and duodenal cellular level.

Topics: Animals; Body Weight; Cholecystokinin; Duodenum; Eating; Feeding Behavior; Growth Inhibitors; Insulin-Like Growth Factor I; Male; Octreotide; Pancreas; Rats; Rats, Inbred Strains

1. The development of endogenous cholecystokinin (CCK) effects on food intake was studied in normal and undernourished growing rats of postnatal day 1-22. 2. Food intake was estimated by recording the gain in body weight before weaning. 3. l-phenylalanine, a potent stimulant of endogenous CCK release, suppressed 30 min food intake in normally nourished pups of day 7-15 or more but not of day 1-6 rats. 4. However, l-phenylalanine did not affect 24 hr gain in body weight day 1-6 or more, rat pups. 5. l-phenylalanine neither suppressed 30 min food intake nor affected 24 hr body weight in day 16-19 or 20-22 undernourished rat pups. 6. The study suggests that the endogenous CCK satiety effects appear early in the second week of postnatal life in normally nourished rats, whereas in undernourished rat pups it does not appear till day 20-22.

Topics: Animals; Body Weight; Cholecystokinin; Diet; Eating; Male; Nutrition Disorders; Nutritional Status; Phenylalanine; Rats; Satiety Response

Bombesin (BBS) has been shown to promote pancreatic growth as well as the development of pancreatic (pre)neoplasia in rats. The present study was carried out to determine the effects of bombesin on pancreatic growth and on the development of pancreatic (pre)neoplastic lesions in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Bombesin caused an increase in growth of the pancreas accompanied by a decrease in the number of (pre)neoplastic ductular pancreatic lesions. Lorglumide (CR-1409) did not influence these effects of bombesin. It is concluded that in BOP-treated hamsters the effect of bombesin on the pancreas is not mediated by cholecystokinin (CCK). These data support the existence of species difference between rats and hamsters with regard to the effect of bombesin on pancreatic carcinogenesis.

Topics: Animals; Body Weight; Bombesin; Cholecystokinin; Cricetinae; Liver; Male; Mesocricetus; Nitrosamines; Pancreas; Pancreatic Neoplasms; Proglumide

It was previously reported that cholecystokinin (CCK) immunization of swine increased food intake 8.2% and rate of growth 10.6%. This report compares carcass yields of lean, fat and bone tissues of CCK-immunized vs. human serum globulin (hSG) control animals. The experiment involved 24 castrated pigs, age 75 d, weight 25.6 kg, randomly assigned to the CCK-immunized or hSG control groups (2 pigs/pen, 6 pens/group). Food was offered for ad libitum access. Carcasses of CCK-immunized animals (vs. hSG controls) were 8.7% heavier (P less than 0.01) and 2.4% longer (P less than 0.01). Carcass yield and composition were analyzed by dissection to lean, fat and bone fractions and by proximate analysis of the resultant lean fraction. Carcasses from the CCK-immunized animals had 2.7 kg more lean (P = 0.09) and 1.8 kg more fat (P = 0.04). Proximate analysis indicated there were no significant differences in composition of the lean fraction. The 7.2% heavier lean fractions of the CCK-immunized animals contained 9.2% more protein (P = 0.09) and 5.1% more fat (P = 0.05). Lean:fat and protein:fat ratios were not significantly altered.

Topics: Animals; Body Composition; Body Weight; Cholecystokinin; Eating; Immunization; Male; Random Allocation; Swine

To determine the type of cholecystokinin (CCK) receptor that mediates the inhibitory effects of peripherally administered CCK-8 on food intake and activity in 9- to 12-day-old rat pups, we gave injections of a type-A CCK receptor antagonist, MK-329, or of the type-B CCK receptor antagonist, L-365,260, prior to CCK-8 (IP). MK-329 reversed the inhibitory effects of CCK-8, but L-365,260 did not. This demonstrates that the inhibitory effects of CCK-8 (IP) are mediated by type-A, but not type-B, CCK receptors in pups of this age.

Topics: Animals; Benzodiazepinones; Body Weight; Cholecystokinin; Devazepide; Feeding Behavior; Female; Motor Activity; Phenylurea Compounds; Pregnancy; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin

In a test of the possible antagonistic interaction between cholecystokinin (CCK) and morphine, morphine-dependent rats were injected with one of three doses of CCK or with naloxone immediately following the consumption of a novel saccharin solution. Whereas opiate-dependent rats injected with the opiate antagonist naloxone acquired an aversion to the saccharin solution (and displayed a dramatic weight loss), CCK was without effect. These data were discussed in relation to the possible pharmacological antagonism between CCK and the opiates.

Topics: Animals; Avoidance Learning; Body Weight; Cholecystokinin; Conditioning, Operant; Drinking; Female; Habituation, Psychophysiologic; Morphine Dependence; Rats; Substance Withdrawal Syndrome

The effect of truncal vagotomy (TV) on pancreatic carcinogenesis initiated with N-nitrosobis(2-oxopropyl)amine (BOP) was investigated in 81 female Syrian golden hamsters. The animals were divided into four groups according to the treatment, groups 1 and 2 serving as non-initiated controls receiving a single s.c. injection of 0.9% NaCl followed by either a sham operation or TV respectively, at week 2. Groups 3 and 4 were given a single s.c. injection of 70 mg/kg body wt of BOP before the sham operation or TV. All hamsters were killed at week 24, and the pancreas, liver and gall bladder tissues were examined histologically. While TV itself caused no significant change in pancreatic weight, the incidence of pancreatic carcinomas in hamsters from group 4 was 48.4%, significantly higher than the 16.7% evident in hamsters from group 3 (P less than 0.05). GLC analysis of the bile acid composition of gall bladder bile from hamsters not receiving carcinogen 1 and 4 months after TV revealed significantly decreased secondary bile acids. The results thus indicated that changes in bile acid composition may be involved in enhancement of BOP-initiated pancreatic carcinogenesis in hamsters by TV.

Topics: Animals; Bile Acids and Salts; Body Weight; Carcinogens; Cholecystokinin; Cricetinae; Female; Gallbladder; Liver; Mesocricetus; Nitrosamines; Pancreas; Pancreatic Neoplasms; Vagotomy, Truncal

We examined in male Sprague-Dawley rats the effects of nicotine at doses of 50 (0.31 mM) and 200 mg/L (1.23 mM) given for a period of 16 weeks on body weight gain, food and fluid intake, plasma CCK, glucose and insulin levels, amylase secretory responses of isolated pancreatic acinar cells to CCK-8 and carbachol, and histopathology (gross and light microscopy) of stomach and pancreas. These parameters were re-examined further in animals treated with nicotine at doses of 200 mg/L (1.23 mM) for 12 weeks and given tap water for an additional 4 weeks to evaluate the effects of nicotine withdrawal. Metabolic data suggest that decreases in body weight gain, food and fluid intake, and plasma levels of glucose and insulin by nicotine are dose dependent. Endocrinological studies showed that the plasma levels of CCK were significantly increased with nicotine but the amylase secretory response of pancreatic acinar cells was inhibited in response to CCK-8 and carbachol. Histopathologic data revealed that treatment of animals with a high dose of nicotine enhanced the appearance of numerous vacuoles in the pancreatic acinar cell cytoplasm. When the pancreatic acinar cell morphology was closely examined, it showed evidence of pyknotic nuclei and fusion of vacuoles. Prominent loss of gastric mucosal surface was found in nicotine-treated animals with gross microscopic evidence of bleeding ulcers. All of the metabolic parameters except body weight gain were reversed upon nicotine withdrawal. In addition, plasma CCK levels and pancreatic enzyme secretion were reversed upon nicotine withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amylases; Animals; Blood Glucose; Body Weight; Cholecystokinin; Digestive System; Drinking; Eating; Insulin; Male; Nicotine; Pancreas; Peptic Ulcer Hemorrhage; Radioimmunoassay; Rats; Rats, Inbred Strains; Stomach Ulcer; Substance Withdrawal Syndrome

We studied the effects of small-bowel resection and bypass on pancreatic function in rats subjected to a 50% distal resection (DR), a 50% proximal resection (PR), a 50% jejunal bypass (BP) or an intestinal transection (SH) (controls). Duodenal contents were collected after cannulation (under basal conditions). Afterwards, an in vivo duodenal perfusion was made using a glucose/saline solution and perfusate was collected for 1 h. Following this, a cholecystokinin (CCK) solution was injected into the jugular vein (1 U/kg body wt.) and perfusion continued for another 1 h. Basal duodenal volume only increased in rats with a PR, and no significant changes occurred in protein content. In basal conditions, no decreases in amylase, lipase, trypsin, or chymotrypsin activities after DR, PR or BP were detected. When animals were subjected to a perfusion and CCK stimulation, no significant changes occurred in animals with BP; the volume was maintained in rats with PR and DR but a decrease in protein and enzymatic contents was found. We concluded that, in basal conditions, the lack (resections) or exclusion (BP) of 50% of the small bowel does not negatively affect the digestive function. When however, a sustained activity is required, the extirpation of intestinal surface provokes a fall in enzymatic activities and is not modified if only the intestinal transit is suppressed, as occurs in the cases of BP.

Topics: Amylases; Animals; Body Weight; Cholecystokinin; Intestine, Small; Jejunoileal Bypass; Lipase; Male; Pancreas; Pancreatic Juice; Rats; Rats, Inbred Strains; Secretory Rate

Cholecystokinin (CCK) has been shown to promote pancreatic growth and azaserine-induced pancreatic carcinogenesis in rats. The present study was carried out to determine effects of CCK on pancreatic growth and carcinogenesis in the N-nitrosobis(2-oxopropyl)amine (BOP) hamster model. One hundred male Syrian golden hamsters were injected s.c. once weekly with 20 mg BOP/kg body wt at 6, 7 and 8 weeks of age, and divided into four groups of 25 animals each, which received one of the following treatments (once daily, 3 days/week for 16 weeks): gelatin; CR-1409, a potent CCK-receptor antagonist; CCK-8, 2.5 micrograms/kg body wt; or CCK-8 in combination with CR-1409 (30 min before CCK treatment). The animals were killed after 19 weeks. The growth of the pancreas but not the incidence of pancreatic (pre)neoplastic lesions was enhanced by CCK-8. CR-1409 did not influence the effect of CCK on pancreatic growth.

Topics: Animals; Body Weight; Carcinogens; Cholecystokinin; Cocarcinogenesis; Cricetinae; Male; Nitrosamines; Organ Size; Pancreas; Pancreatic Neoplasms; Proglumide

Cholecystokinin (CCK) gene expression has been compared in the brain and duodenum of control and 5 days fasted rats. To study transcription, CCK mRNA was quantified using a solution hybridization assay. Large and small molecular weight CCK peptides were separated using a sequential extraction process and subsequently quantified by radioimmunoassay. In the duodenum, a fall in weight was paralleled by a decrease in CCK mRNA and in the large forms of CCK peptides. Small molecular species of CCK peptides did not change. There was no change in weight, CCK transcriptional or translational products in the brain as a whole. These data indicate location-specific differential regulation of the products of CCK gene expression in the fasted rat.

Topics: Animals; Body Weight; Brain; Cholecystokinin; Down-Regulation; Duodenum; Fasting; Gene Expression; Nucleic Acid Hybridization; Organ Size; Protein Biosynthesis; Rats; Rats, Inbred Strains; RNA Probes; RNA, Messenger; Transcription, Genetic

1. The effect of lorglumide, a new potent cholecystokinin (CCK) antagonist, on pancreatic secretion and growth induced by caerulein and bombesin was studied in the rat. 2. Pancreatic exocrine secretion was studied both in vitro (isolated and perfused pancreatic segments) and in vivo (anaesthetized animals with cannulation of the common bile duct) whereas the trophic effect was investigated after short-term (5 days) administration of the peptides and/or lorglumide. 3. Both caerulein and bombesin stimulated amylase release from in vitro pancreatic segments in a concentration-dependent manner. Although the efficacy of both peptides was virtually identical, the potency of caerulein was higher than that of bombesin. Lorglumide displaced the concentration-response curves to caerulein to the right without affecting the maximum response, suggesting a competitive antagonism. The Schild plot analysis of data gave a straight line with a slope not significantly different from unity. The calculated pA2 for lorglumide was 7.31 +/- 0.45. The antagonist, however, was completely ineffective when tested against bombesin-induced amylase release. 4. In vivo experiments confirmed results from in vitro studies since lorglumide (5 and 10 mg kg-1) significantly reduced pancreatic exocrine secretion induced by caerulein without affecting the response to bombesin. 5. Administration of either peptide increased the weight of the pancreas, the total pancreatic protein and DNA, trypsin and amylase content. Lorglumide (10 mg kg-1), administered together with caerulein, reduced the peptide-induced increase in pancreatic weight, protein and enzyme content. On the contrary, when lorglumide was given together with bombesin, all the parameters that were examined were not altered by concomitant administration of the antagonist. 6. These results have demonstrated the ability of lorglumide to antagonize the effects on the pancreas of a CCK-analogue, caerulein, and its inability to affect bombesin-induced pancreatic secretion and growth, suggesting that lorglumide is a potent and selective antagonist of CCK-receptors in the pancreas.

Topics: Amylases; Anesthesia; Animals; Body Weight; Bombesin; Ceruletide; Cholecystokinin; DNA; Glutamine; In Vitro Techniques; Male; Pancreas; Proglumide; Rats; Rats, Inbred Strains; Trypsin

Pancreatic adaptation following prolonged exposition to growth promoting conditions (protease inhibitor feeding, B II subtotal gastrectomy, subtotal colectomy) was studied in rats. Fifty male Wistar rats were divided into 5 groups: controls (n = 10), sham-operated (n = 10), low dose protease inhibitor feeding (n = 10), B II subtotal gastrectomy (n = 10), and subtotal colectomy (n = 10). After 4 mo a significant increase in pancreatic wet wt and DNA content was observed in rats after protease inhibitor feeding (p less than 0.01), B II gastrectomy (p less than 0.01), and subtotal colectomy (p less than 0.05). Pancreatic total protein and lipase content were significantly increased in these three groups. Amylase and trypsin content increased after feeding the protease inhibitor (p less than 0.01) and following B II subtotal resection (p less than 0.01) but were unaffected after subtotal colectomy. Comparing the long-term effects (4 mo) with our previously published short-term data (4 wk) under the same experimental conditions, pancreatic trophism after 4 mo is less pronounced but characterized by a change in the enzyme composition with an increase in pancreatic lipase content.

Topics: Adaptation, Physiological; Amylases; Animals; Body Weight; Cholecystokinin; Colectomy; DNA; Gastrectomy; Lipase; Male; Organ Size; Pancreas; Protease Inhibitors; Proteins; Rats; Rats, Inbred Strains; Time Factors; Trypsin

The role played by the polyamines in mediating the pancreatic growth and secretory responses to hormonal stimulation is uncertain. The effect of an inhibitor of ornithine decarboxylase (ODC), alpha-difluoromethylornithine (DFMO), on rat pancreatic protein secretion and synthesis and on growth in response to hormonal stimulation was therefore studied. Anesthetized rats were given an intravenous injection of DFMO (50, 100, or 150 mg/kg), followed by a 7-h continuous infusion (15, 25, or 35 mg/kg/h, respectively). After a basal 1-h period an intravenous infusion of 2.5 micrograms/kg/h of the cholecystokinin-like peptide Thr28Nle31CCK25-33 (CCK-LP) was added and continued for 6 h. The control rats received CCK-LP only. The ODC activity in the pancreas was markedly reduced by DFMO, but DFMO did not affect pancreatic juice volume or protein output. In another series conscious rats were given a continuous intravenous infusion of 2.5 micrograms/kg/h of CCK-LP for 8, 24, and 48 h or 5.0 micrograms/kg/h of secretin for 8 and 48 h, with or without DFMO (100 mg/kg as an injection initially and thereafter 25 mg/kg/h). The ODC activity and putrescine concentration in the pancreas were significantly reduced by DFMO at 8 and 24 h but not at 48 h. DFMO also significantly reduced the activities of RNA polymerase, DNA polymerase, and thymidine kinase at 24 h, but not at 48 h. The present study thus indicates that polyamines play a role in the initiation of the growth response to hormonal stimulation but does not support a similar dependence for early pancreatic protein synthetic and secretory responses.

Topics: Animals; Body Weight; Cholecystokinin; DNA; Eflornithine; Infusions, Intravenous; Male; Organ Size; Pancreas; Polyamines; Proteins; Rats; Rats, Inbred Strains; RNA

This study was undertaken in male Sprague-Dawley rats to test the hypothesis that chronic ingestion of a low dose of nicotine suppresses body weight gain. The results from this study suggest that chronic nicotine ingestion induces weight loss in rats without the loss of their food intake. To determine whether the nicotine-induced body weight reductions are associated with endocrinological changes, the levels of gastrin and CCK in plasma were measured by specific radioimmunoassays and were found significantly elevated during chronic ingestion of nicotine. The data indicate that reduction of body weight mass by nicotine might be dependent on both hormonal and metabolic factors.

Topics: Animals; Body Weight; Cholecystokinin; Feeding Behavior; Gastrins; Male; Nicotine; Rats; Rats, Inbred Strains; Time Factors

The effects on the pancreas of chronic (95 wk) dietary exposure to protease inhibitors from soy and potato were compared in rats and mice. Soy and potato trypsin inhibitor (TI) concentrates were prepared from defatted raw soy flour and potato juice, respectively, by selective precipitation and ultrafiltration. Animals were fed a diet in which casein supplied approximately 20% protein. Each concentrate (less than 1% of the diet) was added to provide 100 and 200 mg of trypsin inhibitor activity per 100 g of diet. In short-term (28 d) experiments in rats, both sources of TI decreased the apparent nutritional quality of casein and produced pancreatic hypertrophy consistent with a hormonally mediated feedback mechanism for pancreatic adaptation to diet that is interactive with the nutritional status of the animal. After long-term feeding (95 wk), soy and potato TI produced dose-related pancreatic pathology in rats consisting of nodular hyperplasia and acinar adenoma, which was typical of that associated with raw soy flour. Although mice responded similarly to rats to soy TI in short-term (28-d) feeding experiments, they were resistant to the formation of these lesions following long-term feeding. This considerable species variation in propensity to develop preneoplastic and neoplastic lesions of the pancreas is not predicted by the short-term hypertrophic and hyperplastic response of the pancreas to TI.

Topics: Adenoma; Animals; Body Weight; Carcinogens; Caseins; Cholecystokinin; Data Interpretation, Statistical; Glycine max; Longitudinal Studies; Male; Mice; Mice, Inbred Strains; Nutritive Value; Organ Size; Pancreas; Pancreatic Neoplasms; Rats; Rats, Inbred Strains; Solanum tuberosum; Trypsin Inhibitors

The effects of cholecystokinin and bombesin on growth of the exocrine pancreas have been studied extensively in rats but not in hamsters. Since hamsters are frequently used for studying pancreatic carcinogenesis it seems highly relevant to determine the effects of these peptides on growth of the hamster pancreas as well. In order to determine whether or not bombesin stimulates pancreatic growth in hamsters and to investigate the role of cholecystokinin in mediating this effect, we conducted a 2-week experiment in which cholecystokinin and bombesin were administered to both rats and hamsters, either with or without lorglumide (CR-1409; a specific cholecystokinin receptor antagonist). Rats were included in the study for comparison. Cholecystokinin and bombesin were found to stimulate pancreatic growth and DNA synthesis in both species. Lorglumide did not significantly influence the effect of bombesin on pancreatic weight but did significantly inhibit DNA synthesis in both species. The effect of cholecystokinin on pancreatic weight was greater in hamsters than in rats. This effect was significantly inhibited by lorglumide in hamsters but not in rats, whereas a significant decrease in DNA content was attained in both species. Thus, this study shows marked differences between rats and hamsters in the pancreatic growth response to cholecystokinin and bombesin.

Topics: Animals; Body Weight; Bombesin; Cholecystokinin; Cricetinae; DNA; Male; Mesocricetus; Pancreas; Proglumide; Proteins; Rats; Rats, Inbred Strains; Species Specificity; Time Factors

Differences in pancreatic responses and CCK release to intragastric administration of a synthetic protease inhibitor (camostate) were examined in young (6-mo) and old (26-mo) female rats. When rats were sacrificed 1 hour after camostate administration (100 mg/kg), plasma CCK concentration significantly increased in both age groups and was significantly higher in young rats than in the old. Acute pancreatic responses to camostate were attenuated in old rats, compared with the young. On the other hand, 5-day administration of camostate (100 mg/kg, twice a day) increased pancreatic wet weight, chymotrypsin concentration and content in pancreas in both age groups, whereas lipase content did not increase in old rats although it significantly increased in young rats. Plasma CCK concentrations were not significantly different between young and old rats. It is concluded that the acute response of CCK release to camostate is attenuated in old rats, but the capability of chronic pancreatic adaptation of chymotrypsin content to camostate is well maintained in old rats.

Topics: Aging; Animals; Body Weight; Cholecystokinin; Dose-Response Relationship, Drug; Esters; Female; Gabexate; Guanidines; Intubation, Gastrointestinal; Lipase; Organ Size; Pancreas; Protease Inhibitors; Rats; Rats, Inbred F344; Secretory Rate; Trypsin

The rat has been a useful model for studying neuronal and metabolic abnormalities associated with fetal and neonatal hypothyroidism produced by treatment of the mother with antithyroid medication. The neonates are then maintained on this medication via the mother's milk until weaning and subsequently through the drinking water. We have determined the concentrations and contents of immunoreactive cholecystokinin (CCK) and vasoactive intestinal peptide (VIP) in the brain and gut of groups of rats exposed to antithyroid medication from day 16 of gestation. The neonates were sacrificed at 2, 4, 8 and 12 weeks. Compared to controls total body weight was greatly reduced in methimazole (MMI)-treated rats, all of whom were hypothyroid as evidenced by marked reduction of T4 and increase in TSH. Discontinuation of MMI-treatment after 8 weeks resulted in normalization of T4 and TSH and a dramatic weight gain but at 12 weeks the brain weights of the MMI-treated rats were reduced by 17% and the brain contents, of CCK and VIP were similarly reduced. Tissue weights throughout the gut were 1/2 or less than those of control rats. Since VIP but not CCK concentrations in the gut of MMI-treated animals were significantly greater than those of the control animals, it would appear that there was greater loss of mucosal tissue with its endocrine content of CCK than of neuronal tissue with its greater content of VIP.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aging; Animals; Animals, Newborn; Body Weight; Brain Chemistry; Cholecystokinin; Digestive System; Female; Hypothyroidism; Methimazole; Organ Size; Pregnancy; Radioimmunoassay; Rats; Rats, Inbred Strains; Vasoactive Intestinal Peptide

It has been shown that the large bowel contains substances with a potential to inhibit exocrine pancreatic function. Following large bowel removal in rats, there is an increase of pancreatic weight, digestive enzyme concentration, and secretion capacity in vitro. To evaluate the role of various GI hormones in the exocrine pancreatic adaptation following colectomy, we measured plasma cholecystokinin (CCK), neurotensin, glucagon, and insulin after meal stimulation. The test meal was applied via a transabdominal gastric tube in eight colectomized Wistar rats after a median of 18 days following surgery. Ten rats with a gastric tube without previous bowel surgery served as controls. After large bowel removal, there was impaired glucose tolerance and attenuated plasma insulin secretion. Baseline plasma glucagon levels were increased after colon removal, whereas the total postprandial glucagon release was decreased. Baseline and postprandial neurotensin values were comparable in both the experimental and control animals. Baseline and postprandial CCK plasma levels were intensely increased in the colectomized rats. It is assumed that the baseline and postprandial CCK pattern in rats after subtotal colectomy is responsible for exocrine pancreatic adaptation.

Topics: Animals; Blood Glucose; Body Weight; Cholecystokinin; Colectomy; Diet; Gastrointestinal Hormones; Glucagon; Insulin; Insulin Secretion; Male; Neurotensin; Pancreas; Rats; Rats, Inbred Strains

The results of our preliminary experience with the gastric balloon program for weight loss in morbidly obese patients are reported. In a pilot project, we measured gastric-acid secretion, gastrin and cholecystokinin (CCK) levels in ten patients before and during balloon therapy in a study of the impact of the balloon on gastric physiology. Gastric-acid secretion tended to decrease following balloon treatment, while gastrin and CCK levels were unchanged suggesting that weight loss is achieved by mechanisms, which are not mediated by gastrin or CCK. The balloon program was then expanded to a group of 29 patients who met the criteria. They were followed for a period of 4 months. Average weight loss for the group was 31 +/- 4 pounds for a monthly average of 8 pounds. The main complications were gastric ulcers in four patients and a small-bowel obstruction in one patient. Satisfactory weight loss was achieved in 80 per cent of patients, but this benefit must be balanced against a relatively high incidence (17%) of side effects, some of which were quite serious. Therefore, the gastric balloon program should still be considered experimental.

Topics: Adult; Body Weight; Cholecystokinin; Female; Gastric Acid; Gastrins; Humans; Male; Middle Aged; Obesity, Morbid; Prospective Studies; Prostheses and Implants

The effect of a chronic administration of cholecystokinin (CCK) on the rat pancreas has been studied in rats subjected to a 90% jejunoileal bypass or an intestinal transection (controls). Jejunoileal bypass, when compared to transection, did not modify the size of the pancreas but decreased its enzyme content, especially for amylase, and reduced the number of zymogen granules. These structural and biochemical changes were maintained when bypassed animals were treated three times daily and for six days with cholecystokinin (20 Ivy Dog Units (IDU)/kg). In contrast, CCK treatment in transected animals induced growth of the pancreas due to cellular hypertrophy and hyperplasia; pancreatic enzyme content, especially for chymotrypsin, and the population of zymogen granules in acinar cells were also enhanced. It is concluded that jejunoileal bypass prevents the trophic action of chronic CCK on the pancreas.

Topics: Animals; Body Weight; Cholecystokinin; DNA; Intestine, Small; Jejunoileal Bypass; Male; Organ Size; Pancreas; Proteins; Rats; Rats, Inbred Strains; RNA

Cholecystokinin (CCK) and Bombesin (BBS) are two neuropeptides which induce changes in monoamines in the brain after peripheral administration. A vagal mediation of these effects was investigated since the satiety responses to both peptides are affected differently by vagotomy. This work was performed on genetically obese and lean Zucker rats and on "cafeteria-fed" and lean Sprague-Dawley rats as the effects of the peptides are dissimilar in these different groups. Vagotomy either inhibited or potentiated the peptide-induced effects, or created new variations. With CCK, the inhibition occurred mainly in the serotonergic system and in the Zucker strain, while new effects appeared in the dopaminergic system of lean rats of both strains. With bombesin, vagotomy inhibited the effects in the dopaminergic system in all lean rats, while new effects were observed in the serotonergic system in the Zucker strain. These data enable the differentiation of the mechanisms of action of both peptides and their selective effects, according to the strain of rat and the presence or absence of obesity.

Topics: Animals; Body Weight; Bombesin; Brain; Cholecystokinin; Female; Neurotransmitter Agents; Obesity; Rats; Rats, Inbred Strains; Rats, Zucker; Vagotomy

While exogenous administration of cholecystokinin (CCK) decreases food intake in many species, it has not been demonstrated conclusively that CCK is necessary for satiety to occur. In these experiments the role of CCK in eliciting satiety was further investigated by using endogenously produced and exogenously administered antibodies to CCK which were hypothesized to sequester circulating CCK. In the first experiment Zucker obese (n = 12, 192 +/- 16 g) and lean (n = 12, 152 +/- 11 g) male rats were administered CCK-8 conjugated to bovine serum albumin or bovine serum albumin by subcutaneous administration in Freund's adjuvant. Average percent binding of 125I-gastrin-17 by serum taken 4, 8 and 12 weeks after treatment initiation was increased (19.9 vs. 2.1, p less than 0.001) in rats treated with CCK conjugate than controls, and the increase was greater in lean (27.5 vs. 1.9) than in obese (12.2 vs. 2.2, p less than 0.001) rats. In lean, but not obese rats, average daily food intake and weight gain were increased (9 and 17% p less than 0.04 and p less than 0.02 respectively) in rats with CCK-AB compared with rats with no CCK-AB during the three months. Development of CCK-AB did not affect food intake response to exogenously administered CCK-8 or pancreas weight relative to body weight. In Experiment 2 increased food intakes of obese and lean rats 30 min after intraperitoneal injection of rabbit serum with CCK-AB were greater than those after intraperitoneal injection of rabbit serum without CCK-AB (1.92 vs. 1.41, g, p less than 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Body Weight; Cholecystokinin; DNA; Eating; Energy Metabolism; Male; Pancreas; Rats; Rats, Zucker; RNA; Satiation

This report deals with the effect of feeding inhibitors of pancreatic and brush border enzymes on pancreatic growth and enzyme composition and secretion. Raw soybean flour containing trypsin inhibitors caused pronounced growth of the pancreas which was accompanied by increased enzyme content and increased CCK and gastrin concentration in the plasma. Feeding of an amylase inhibitor to a starch-rich diet induced a marked fall in amylase content and secretion without changing growth parameters of the pancreas, indicating that not starch but glucose is the trigger for the maintenance of amylase content and secretion of the pancreas. The addition of an alpha-glucosidase inhibitor (acarbose) to a sucrose- or maltose-rich semisynthetic diet did not cause significant alteration in pancreatic growth or enzyme composition or secretion. In man pancreatic function was also unaltered by 8 weeks' intake of 3 X 200 mg acarbose.

Topics: Acarbose; Adaptation, Physiological; alpha-Amylases; Amylases; Animals; Blood Proteins; Body Weight; Cholecystokinin; Diet; DNA; Enzyme Inhibitors; Gastrins; Glycine max; Glycoside Hydrolase Inhibitors; Humans; Male; Oligosaccharides; Organ Size; Pancreas; Rats; Rats, Inbred Strains; Trisaccharides; Trypsin Inhibitors

This work investigates the effect, on the rat pancreas, of a chronic administration of bombesin in function of the dose and duration of treatment and examines whether this effect may be mediated by the release of endogenous gastrin or cholecystokinin. Bombesin, administered three times daily for 5 or 15 days, induced a marked increase in pancreatic weight, its protein, RNA and enzyme contents with the dose of 10 micrograms/kg body weight; the ratios of pancreatic weight, protein and RNA contents to DNA contents increased significantly after a 5 day treatment, suggesting cellular hypertrophy. Pancreatic DNA content was markedly enhanced after a 15 day treatment, suggesting cellular hyperplasia. Antrectomy decreased plasma gastrin levels, but did not alter the pancreatico-trophic action of a 10 micrograms/kg bombesin treatment for 5 days. Proglumide, an inhibitor of cholecystokinin and gastrin in the pancreas, did not affect the growth of the pancreas induced by a 10 micrograms/kg bombesin treatment for 5 days. It is concluded that chronic bombesin induces, in the rat pancreas, cellular hypertrophy or hyperplasia depending on the duration of treatment. Pancreatic hypertrophy is not mediated by the release of endogenous gastrin or cholecystokinin.

Topics: Amylases; Animals; Body Weight; Bombesin; Cholecystokinin; Chymotrypsin; Gastrectomy; Gastrins; Lipase; Microscopy, Electron; Organ Size; Pancreas; Proglumide; Rats; Receptors, Cell Surface; Receptors, Cholecystokinin; RNA

Gastrointestinal polypeptide hormones regulate growth of various normal gastrointestinal tissues as well as certain visceral cancers. Since cholecystokinin (CCK) promotes growth of normal biliary tract, we sought to determine whether CCK affects the growth and metabolism of human cholangiocarcinoma line SLU 132. Twenty-six nude mice with s.c. xenografts of this cancer received either CCK octapeptide (50 micrograms/kg/dose) or 0.9% NaCl solution (saline) twice a day i.p. for 14 days. Tumor volume was calculated from Vernier caliper measurements. At sacrifice on Day 15, tumors were excised, weighed, and examined histologically. DNA, RNA, and protein were measured in the xenografted carcinomas. Because this cholangiocarcinoma produces carcinoembryonic antigen (CEA), we obtained serum at sacrifice for CEA radioimmunoassay and also tumor tissue for CEA immunolabeling with murine anti-CEA monoclonal antibody. Serum CEA levels were 90% higher in the CCK-treated group. Tumor tissue in the CCK-treated group also contained more CEA than did the controls. Mean tumor volume increased significantly in the saline group during the 14-day treatment period, whereas mean tumor volume did not increase significantly in the CCK group. Exogenous high-dose CCK thus appears to increase production and release of CEA from SLU-132; it also appears to retard growth of this tumor line in the nude mouse.

Topics: Adenoma, Bile Duct; Aged; Animals; Bile Duct Neoplasms; Body Weight; Carcinoembryonic Antigen; Cholecystokinin; Humans; Male; Mice; Mice, Nude; Neoplasm Transplantation; Transplantation, Heterologous

The cellular localization and regional distribution of peptides of the gastrin/cholecystokinin family was investigated in human fetal, neonatal and adult brains by use of immunohistochemical techniques. It could be revealed that a cholecystokinin-like immunoreactivity is already present in human brain at the 11/12th gestational weeks. With the 19th week a strong increase in number of CCK reactive cells and the reaction intensity is obvious. The data are compared with the distribution pattern of the adult brain. Our data permit to conclude that gastrin/CCK-related material might play roles independent of neurotransmitter functions during early human brain development.

Topics: Aged; Body Weight; Brain; Brain Chemistry; Cholecystokinin; Female; Fluorescent Antibody Technique; Gestational Age; Humans; Immunoenzyme Techniques; Infant, Newborn; Male; Pregnancy; Spinal Cord

Cholecystokinin, secreted when ingested food enters the duodenum, may act as a satiety factor. Injection of proglumide, a specific antagonist of cholecystokinin, induced an increase in food intake. The satiety effect of administered cholecystokinin is abolished by bilateral subdiaphragmatic vagotomy. If endogenous and exogenous cholecystokinin act via the same mechanism, then vagotomy should abolish the proglumide-induced increase in food intake. Proglumide was used to block the satiety effect of a food preload in sham-operated and vagotomized rats. Proglumide induced an increase in food intake in sham-operated rats confirming earlier results. No change in meal size was observed in vagotomized rats following proglumide injection. These results suggest that vagotomy abolishes the effect of endogenous cholecystokinin on food intake. However, evidence of dumping in vagotomized rats prevents the interpretation of the data as a direct vagal involvement in endogenous CCK-induced satiety.

Topics: Animals; Appetite; Body Weight; Cholecystokinin; Energy Intake; Glutamine; Male; Proglumide; Rats; Rats, Inbred Strains; Vagotomy

Plasma concentrations of gastrointestinal hormones were measured by radioimmunoassay in fasted rats 9 days after infection with a range of doses of Nippostrongylus brasiliensis. Values for infected rats fed ad libitum were compared with those of weight matched, pair fed, uninfected rats to control for the possible effects of dose-dependent reductions in food intake associated with infection. The plasma concentrations of some of the gastrointestinal hormones in infected rats were very different from those of their pair fed partners. The magnitude and direction of the changes varied according to the hormone being examined. Plasma concentrations of gastrin and pancreatic polypeptide were similar in pair fed and infected rats at all doses used. For the other hormones assayed, infection was associated with dose-related changes. The plasma concentrations of cholecystokinin and insulin were slightly but significantly reduced in infected rats. In contrast, secretin, enteroglucagon, and pancreatic glucagon concentrations were markedly increased. At the highest dose given (52 larvae/g body wt), the plasma levels of secretin and enteroglucagon in infected rats were elevated 9 X and 15 X, respectively. A comparison of the changes seen in N. brasiliensis-infected rats with those reported for other helminth infections revealed striking differences. The possible etiology of alterations in plasma gastrointestinal hormone concentrations and their contribution to the pathological changes seen in animals infected with helminths are discussed.

Topics: Animals; Body Weight; Cholecystokinin; Energy Intake; Gastrins; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptides; Male; Nematode Infections; Nippostrongylus; Pancreatic Polypeptide; Rats; Secretin

Topics: Animals; Antifungal Agents; Body Weight; Cerulenin; Cholecystokinin; DNA; Ethionine; Male; Microscopy, Electron; Organ Size; Pancreas; Pancreatic Juice; Rats; RNA

Topics: Animals; Body Weight; Cholecystokinin; Eating; Endorphins; Hypothalamic Area, Lateral; Hypothalamus; Hypothalamus, Middle; Neural Pathways; Neurotransmitter Agents; Paraventricular Hypothalamic Nucleus; Peptides; Rats; Receptors, Cell Surface; Reward; Satiation; Self Stimulation; Stomach

Rats were given subcutaneous injections of synthetic cholecystokinin octapeptide (CCK8, 5 micrograms/kg) in a depot carrier twice daily for 7-14 days. The pancreatic wet weight increased by 20.6 and 30.9% in the rats treated with CCK8 for 7 and 14 days, respectively. The increase in pancreatic weight was associated with an increase in the amount of protein per DNA, indicating hypertrophy of the acinar cells, and with an increase in the total amount of pancreatic DNA. Moreover, CCK administration also increased the amylase content per DNA. In acini prepared from CCK8-treated rats, responsiveness to CCK8 was increased when amylase release was expressed relative to DNA but was decreased when calculated as the percentage of the initial content in the acini. The dose-response curves for CCK8 were similarly shaped in both CCK8-treated and control rats, but they were shifted 3- to 10-fold toward higher concentrations of CCK8 after 7 and 14 days of CCK8 treatment. There were no major changes in the affinity and capacity of CCK receptors determined by studying the binding of radioiodinated CCK, suggesting that alterations in pancreatic amylase release were due to changes at a postreceptor loci. In support of this hypothesis, the secretory response to carbachol, known to act on a different receptor but by a common intracellular mechanism, was altered in a manner identical to the response to CCK8. Thus chronic stimulation with CCK sufficient to induce pancreatic hypertrophy does not greatly alter CCK receptors and induces only moderate postreceptor desensitization.

Topics: Amylases; Animals; Appetite Depressants; Body Weight; Calcimycin; Carbachol; Cholecystokinin; Kinetics; Male; Organ Size; Pancreas; Peptide Fragments; Rats; Rats, Inbred Strains; Sincalide

Cholecystokinin (CCK) acts acutely to inhibit food consumption in fasted rats, mice, sheep, pigs, monkeys and humans. CCK has been proposed as a satiety signal, inducing the behavioural sequence of satiety, or as an aversive internal stimulus, which inhibits food intake by inducing malaise. Reductions in food intake and related exploratory behaviours are initiated by CCK at its peripheral receptor in the gut, which appears to transmit sensory feedback via the vagus nerve to brain regions mediating appetitive behaviours. The therapeutic potential of CCK as an appetite suppressant in obesity syndromes rests on the demonstration of significant, long-lasting body weight reduction. Chronic CCK administration by repeated injections is problematic, since this peptide is rapidly degraded in vivo. We chose the Alzet constant infusion osmotic minipump to investigate possible alterations in body weight and food intake during continuous infusion of CCK. We now report that no change was detected in either body weight or total daily food consumption at any time point during 2 weeks of intraperitoneally (i.p.) infused CCK. The mechanism underlying the lack of chronic CCK effects appears to be a rapid development of behavioural tolerance. Acute challenge doses of CCK which induced satiety-related behaviours in saline-infused rats were ineffective in CCK-infused rats. The behavioural tolerance was apparent within a few hours of minipump implantation. These results provide the first evidence that rapid and reversible tolerance develops to the actions of a gut peptide.

Topics: Animals; Appetite Depressants; Body Weight; Cholecystokinin; Drug Tolerance; Feeding Behavior; Male; Peptide Fragments; Rats; Rats, Inbred Strains; Sincalide

Cholecystokinin and secretin are believed to be trophic gastrointestinal hormones. Studies were designed to determine whether these hormones exert their effect through stimulation of endogenous secretion. First, four groups of parenterally nourished rats underwent bypass of the proximal two-thirds of the intestine. One group received secretin, another cholecystokinin octapeptide (CCK-OP), another CCK-OP plus secretin, while the fourth group served as control. After 1 wk, animals were killed; pancreas and segments of intestine were removed. First, mucosal weight, protein content, and fatty acid esterification activity were affected only in intestine in continuity with endogenous secretions after hormone administration. Second, the effects of these hormones were tested in chow-fed rats. The hormone-treated group, despite pancreatic hyperplasia, had similar indexes of intestinal mass compared with pair-fed controls. We conclude that CCK-OP and secretin mediate their trophic effects on the small intestine indirectly, probably through stimulation of pancreatic secretion. In addition, the effects of luminal nutrients have complex interactions with these hormones.

Topics: Animals; Body Weight; Cholecystokinin; Duodenum; Ileum; Intestinal Mucosa; Intestine, Small; Jejunum; Male; Organ Size; Pancreas; Peptide Fragments; Rats; Rats, Inbred Strains; Secretin; Sincalide

The effect of long-term dietary modification on pancreatic exocrine function in rats has been investigated by examining responses to cholecystokinin-pancreozymin stimulation, using a method of direct pancreatic duct cannulation. Residual pancreatic enzyme activity remaining in the whole pancreas following stimulation was also measured. After 6 months of dietary modification, changes in the pancreatic secretions of high-protein- or high-fat-fed animals were similar to those reported in short-term studies in which elevation of trypsin and lipase activity occurred in the pancreas. However, between 6 and 9 months, both volume and amylase activity of pancreatic secretions decreased in animals fed a high-protein diet. At 6 and 9 months, animals fed a high-carbohydrate diet had increased amounts of amylase and decreased trypsin in both pancreatic secretion and homogenate, similar to short-term changes previously reported. High-carbohydrate-fed animals had decreased lipase activity in pancreatic secretions, but lipase activity in pancreatic homogenates was increased, similar to levels found in animals fed a high-fat diet.

Topics: alpha-Amylases; Animals; Body Weight; Cholecystokinin; Diet; Dietary Carbohydrates; Dietary Fats; Dietary Proteins; Lipase; Organ Size; Pancreas; Pancreatic Function Tests; Rats; Rats, Inbred Strains; Stimulation, Chemical; Time Factors; Trypsin

Decreased body weight and increased pancreas weight which occur in rats fed raw soybeans are thought to be due to the presence of trypsin inhibitors in the soybeans (SBTI). Since trypsin is postulated to be a negative feedback signal for cholecystokinin (CCK) secretion, SBTI may have these effects by increasing secretion of CCK. CCK is a putative satiety signal; thus, increased secretion of CCK could decrease food intake, and, if maintained over a period of time, body weight. In these experiments the effects of a trypsin inhibitor [N,N-dimethyl-carbamoyl 4-(4-guanidino-benzylyloxy)-phenyl acetate methane-sulfate (DGPM)]on feeding pattern were investigated in Zucker obese and lean rats. Administration of 25-200 mg/kg DGPM to 6-hr fasted rats decreased daily food intake by dose-dependently decreasing average meal size in both obese and lean rats, but the response was greater in obese rats. Administration of 100 mg/kg DGPM twice daily for 7 days decreased food intake and body weight in obese but not lean rats. Thus, these results suggest that decreased body weight associated with SBTI is due to decreased food intake partly as a result of increased secretion of the putative satiety peptide CCK.

Topics: Animals; Body Weight; Cholecystokinin; Eating; Female; Guanidines; Male; Rats; Rats, Zucker; Satiation; Time Factors; Trypsin Inhibitors

The development of cholecystokinin satiety effects was studied in newborn rats. Weight gain during tests was the measure of intake in the sucklings, until the rats were weaned at 20 days of age. Thereafter food intake was measured directly. Intraperitoneal injection of cholecystokinin (CCK-OP) suppressed feeding in 1-7 day old rat pups. Gastric loads of 0.9% NaCl, 2.5% D-phenylalanine, and L-phenylalanine suppressed subsequent intake in 1-10 day old rats, but not in 10-20 day old rats. The early satiety effect of the intragastric loads was attributed to gastric distension. At 21-25 days of age, rats showed a suppression of intake following gastric loads of L-phenylalanine but not D-phenylalanine. This is tentative evidence that releasers of endogenous CCK do not induce satiety until immediately after weaning.

Topics: Aging; Animals; Animals, Newborn; Body Weight; Cholecystokinin; Feeding Behavior; Female; Male; Phenylalanine; Rats; Stereoisomerism

Repeated subcutaneous injections of cholecystokinin octapeptide (CCK-OP) to Syrian golden hamsters for 10 days elicited a marked trophic effect on the pancreas, characterized by increased pancreatic weight and increased RNA/DNA ratios with an enhanced content of amylase in the pancreas in treated hamsters. These responses were observed after relatively small doses (100--300 ng CCK-OP x day-1 . 100 g body weight-1) of the hormone over a 10-day period. Although there was a small increase in total pancreatic DNA there was no definite evidence of hyperplasia in response to CCK-OP. DNA synthesis, as measured by histoautoradiography of tritiated thymidine labelled tissues, was increased in pancreatic acinar and islet cells, but not in ductal cells. This investigation, therefore, demonstrates a trophic action of CCK on the pancreas of the hamster similar to that reported for the rat and this may have relevance in studies of carcinogenesis since the hamster is an established species for studying pancreatic cancer.

Topics: Amylases; Animals; Body Weight; Cholecystokinin; Cricetinae; DNA; Male; Mesocricetus; Organ Size; Pancreas; Peptide Fragments; RNA; Sincalide

Cholecystokinin (CCK), one of the peptides secreted by the gastrointestinal tract during a meal, stimulates release of enzymes into pancreatic juice and is a trophic hormone for the pancreas. Administration of CCK also decreases food intake, and obese rats have been shown to have a higher threshold than lean rats for this apparent effect on satiety. In this study experiments were designed to compare the sensitivity of obese and lean rats to the effects of CCK octapeptide (CCK-8) on pancreatic structure and exocrine function. In both growing and adult Zucker rats DNA content of the pancreas from obese rats was decreased compared with that from lean rats [2.42 +/- 0.21 vs. 3.07 +/- 0.18 mg (P less than 0.01) and 2.46 +/- 0.25 vs. 3.01 +/- 0.19 mg (P less than 0.05), respectively], and in adult obese rats this was accompanied by decreased pancreas size on both absolute weight and percent of body weight bases. In adult obese Bar Harbor mice, although DNA content of the pancreas was also decreased [1.70 +/- 0.10 vs. 2.41 +/- 0.11 mg (P less than 0.01)], pancreas weight was not different (0.30 +/- 0.01 vs. 0.32 +/- 0.01 g). In young rats growth of the pancreas was stimulated by 2 micrograms/kg CCK-8 administered subcutaneously or 100 mg/kg of a trypsin inhibitor administered orally twice daily for 2 wk. Although both treatments increased weight and DNA and protein content of the pancreas, the increases in DNA and protein content were smaller in obese than lean rats, indicating a decreased responsiveness to both trophic agents. Administration of CCK-8 stimulated smaller increases in pancreatic juice volume and amylase release in obese compared with lean rats, indicating decreased pancreatic exocrine function in response to CCK. In adults the CCK-8 dose-response curve for amylase release from dispersed pancreatic acini of obese rats was similar to that of lean rats, indicating normal sensitivity in vitro. Thus, in obese rats and mice DNA content of the pancreas is decreased when compared with that of lean rats and mice, and this is accompanied by decreased in vivo responses to CCK in obese rats.

Topics: Animals; Body Weight; Cholecystokinin; DNA; Eating; Obesity; Organ Size; Pancreas; Proteins; Rats; Rats, Zucker; RNA; Trypsin Inhibitors

Topics: Animals; Body Weight; Bombesin; Cholecystokinin; Eating; Female; Mice; Mice, Obese; Pancreatic Polypeptide; Peptides; Satiation; Satiety Response; Sincalide

Levels of gastrin-cholecystokinin-like immunoreactivity were measured in three brain regions (cortex, diencephalon, brainstem) and the pituitary gland in groups of genetically obese Zucker rats and their non-obese littermates. The obese animals had significantly increased body weights and significantly lowered brain weights. However, levels of gastrin-cholecystokinin-like immunoreactivity were not different between the two groups in any of the regions measured. These results contrast with a recent report [11] in which ob/ob mice were found to have decreased levels of cholecystokinin in their brains.

Topics: Animals; Body Weight; Brain Chemistry; Brain Stem; Cerebral Cortex; Cholecystokinin; Diencephalon; Gastrins; Male; Obesity; Organ Size; Pituitary Gland; Radioimmunoassay; Rats; Rats, Inbred Strains; Species Specificity; Tissue Distribution

Topics: Animals; Body Weight; Brain; Cholecystokinin; Fasting; Mice; Mice, Inbred C3H

Topics: Animals; Body Weight; Cholecystokinin; Dose-Response Relationship, Drug; Drinking; Eating; Exploratory Behavior; Genotype; Male; Mice

Topics: Animals; Body Weight; Bombesin; Cholecystokinin; Eating; Female; Male; Obesity; Peptides; Rats; Weaning

Rats were given subcutaneous injections of secretin (12.5 microgram kg-1) plus caerulein (0.5 microgram kg-1) in a depot carrier or depot carrier alone every 8 hr for 10 days. Basal pancreatic secretion and responses to secretin and cholecystokinin were then studied while the rats were under urethane anesthesia. In the treated animals, basal secretion of fluid was more than six times greater, basal bicarbonate output more than three times greater, and and basal protein output more than two times greater than in the control rats (P less than 0.01 for each). After subtracting basal values and normalizing for body weight, the treated group means were statistically significantly greater than those of the control for: maximal bicarbonate output (1.81 times control) to secretin; and maximal outputs to cholecystokinin of volume (2.46 times control), bicarbonate (2.69 times control), and protein (2.28 times control). The mean pancreatic weight per kilogram of body weight in the treated group was 1.65 times (P less than 0.01) that of the control group. When normalized for pancreatic weight (basal values subtracted), the increse in maximal protein output (1.37 times control) to cholecystokinin was still statistically significant (P less than 0.05). We conclude that chronic treatment with secretin plus caerulein exerts a trophic effect on the pancreas associated with increased maximal protein output to cholecystokinin and increased maximal bicarbonate output to secretin.

Topics: Animals; Bicarbonates; Body Weight; Ceruletide; Cholecystokinin; Female; Organ Size; Pancreas; Proteins; Rats; Secretin

Rats were given soybean trypsin inhibitor or repeatedly injected with pancreozymin (daily 40 I.D.U./kg) for 7 days, and the insulin and glucagon contents of the pancreas were measured. The insulin and glucagon contents were markedly increased after these treatments and this effect was especially conspicuous after injections of large doses (daily 120 I.D.U.) of depot-type pancreozymin. Insulin content thus reached 1.9 times, and glucagon content 2.4 times as much in control values. This result is compatible with our previous histological finding that not only the exocrine pancreas but also islet cells undergo the trophic effect of endogenous and exogenous pancreozymin.

Topics: Administration, Oral; Animals; Body Weight; Cholecystokinin; Glucagon; Injections, Subcutaneous; Insulin; Male; Organ Size; Pancreas; Rats; Trypsin Inhibitors

The hyperphagia characteristic of some types of obesity may result from a deficiency in one or more components of the systems controlling satiety which in rats may include the gastrointestinal hormone cholecystokinin (CCK). Obesity may also influence responsivity to often used central nervous system (CNS)-acting drugs and combination of drugs. In these experiments it was shown that: (1) Zucker fatty rats were less sensitive than lean to intraperitoneal injections of 20 U/kg CCK after a 6-hr fast and when reduced were less sensitive than lean and less sensitive than when obese to injections of 5 U/kg CCK; (2) Although fatties were equally sensitive as leans to injections of 0.5 and 1.0 mg/kg d-amphetamine sulfate, when reduced, they were less sensitive; (3) Injections of 1.25 and 2.5 mg/kg diazepam produced smaller increases in food intake after a 6-hr fast in fatty and reduced fatty than lean rats; (4) Combination of diazepam with cholecystokinin in both fatty and lean rats produced feeding similar to that following injection of carrier; and (5) A similar additive effect was obtained in both fatty and lean rats when diazepam was combined with amphetamine; however, the fatty appeared to be more sensitive to the amphetamine than the diazepam effect. Thus the Zucker fatty rat appears to be less sensitive to these chemicals which affect food intake, which supports the contention that their CNS is generally less responsive.

Topics: Animals; Body Weight; Cholecystokinin; Dextroamphetamine; Diazepam; Drug Interactions; Feeding Behavior; Female; Male; Obesity; Rats; Time Factors

The rate of gastric emptying was determined in three-day old suckling rats. The gastric loads were given by gavage, and, after from 5 to 100 min, emptying was determined by removing the stomach and weighing the contents. Results were expressed as percentage of load still remaining in the stomach at one hour. The gastric loads in increasing order of speed of emptying were 1.0 M Na acetate, heavy cream, 0.5 M NaCl, milk, corn oil, 0.15 M lactose, 0.3 M glucose, 0.15 M NaCl, acidic water, and water. The rate of emptying was compared to the effectiveness in previous experiments of the same gastric loads in depressing intake. There was no significant correlation between rate of gastric emptying of the loads and their effectiveness in producing satiety. The octapeptide of cholecystokinin (80 Ivy dog units or 2.7 micrograms/kg i.p.) significantly depressed intake (measured as weight gain) of suckling rats of 1 1/2 hours, but the same dose did not slow gastric emptying. These findings indicate that rate of gastric emptying does not determine satiety in the suckling rat.

Topics: Animals; Animals, Suckling; Body Weight; Cholecystokinin; Deoxyglucose; Eating; Female; Gastric Emptying; Gastric Juice; Male; Phenylalanine; Rats; Satiety Response

43 gastroenterologically healthy infants and children were investigated during the basic secretion period and after the injection of secretin/pankreozymin in order to establish the total quantity and also the distribution of the secreted bile acids. The total concentration and quantity were enzymatically determined while column and thin-layer chromatography were utilized to separate the bile into 34 different bile acids. Quantified results for bile salts were read directly from the thin-layer sheet with the help of a Chromatogram-Spectrophotometer Zeiss KM 3. While the total quantity of bile acids was found to be independent of age, the composition of bile changed during the first years of life. The percentage of cholic acids decreased from 50% in infants to 35% in older children. At the same time, deoxycholic acids went up from 3% to 13%, and chenodeoxycholic acids increased by 5%. The percentage of glycine and taurine conjugated bile salts, however, remained constant after to the second month of life, the former at 58% and the latter at 35%. In comparison, rather small amounts of unconjugated acids and sulfates were secreted, 0,5% and 6% respectively. The latter were distributed in the same sequence as the nonsulfated bile acids. Lithocholic acids (2,6%) and ursodeoxycholic acids (4,3%) were regularly present in the intestinal secretion.

Topics: Age Factors; Bile Acids and Salts; Body Weight; Child; Child, Preschool; Cholecystokinin; Humans; Infant; Intestinal Secretions; Reference Values; Secretin

Pentagastrin (1.5 mg/kg), 20% pure natural cholecystokinin (CCK, 37.5 Ivy dog U/kg) or secretin (25 microgram/kg) was given in a depot carrier subcutaneously to rats 3 times daily for 15 days. The dose of CCK and secretin was submaximal for pancreatic secretion, whereas the dose of pentagastrin was supramaximal for gastric acid secretion. The pancreatic wet weight increased by 12% (P less than 0.01) in the rats treated with pentagastrin, 57% (P less than 0.001) in those treated with CCK, and 9% (P less than 0.01) in those treated with secretin. In CCK-treated rats, the maximal protein and bicarbonate outputs in response to cholecystokinin increased proportionately to the increase in pancreatic weight, but maximal bicarbonate and protein outputs in response to secretin were unaltered. The secretin-treated rats showed a lowered basal secretion of bicarbonate and a lowered sensitivity to secretin stimulation, but the maximal bicarbonate and protein outputs to secretin and CCK were unchanged. Treatment with pentagastrin produced no significant changes in pancreatic responses to secretin or CCK. We conclude that 1) the increase in pancreatic weight produced by repeated injections of cholecystokinin was accompanied by proportional increase in functional capacity as reflected by the increased maximal bicarbonate and protein outputs in response to cholecystokinin, and 2) repeated administration of secretin decreased the sensitivity of the pancreas to secretin without altering maximal bicarbonate response.

Topics: Animals; Bicarbonates; Body Weight; Cholecystokinin; Duodenum; Gastric Mucosa; Injections, Subcutaneous; Intestinal Mucosa; Islets of Langerhans; Male; Organ Size; Pancreas; Pentagastrin; Rats; Secretin

Repeated injections of cholecystokinin (CCK) during a period of up to 3 weeks significantly increased the weight of the pancreas in rats. This was associated with an increase in the amount of protein per unit weight of DNA, suggesting hypertrophy of the acinar cells, and with increase in the total amount of pancreatic DNA, indicating additional hyperplasia of the gland. CCK administration also increased the pancreatic content of amylase and trypsin, but the content of lipase remained unchanged. The rate of secretion of the two enzymes increased in the CCK-treated rats, although it appeared that the functional capacity of the individual pancreatic acinar cells was not increased. CCK injections had no effect on the insulin content of the pancreas or on the composition of the partoid glands. Repeated injections of secretin in the doses used in this study had no effect on the pancreas.

Topics: Amylases; Animals; Body Weight; Cholecystokinin; DNA; Injections, Subcutaneous; Lipase; Male; Organ Size; Pancreas; Parotid Gland; Rats; Secretin; Stimulation, Chemical; Time Factors; Trypsin

Topics: Aging; Amylases; Animals; Body Weight; Cholecystokinin; Chymotrypsin; DNA; Hyperplasia; Hypertrophy; Lipase; Organ Size; Pancreas; Proteins; Rats; RNA; Stimulation, Chemical

Studies were undertaken in 40 patients with chronic pancreatitis six months to seven and a half years (mean 25 months) after operation, results being compared with pre-operative findings. Measurements included: exercise capacity, absence of pain, body weight, endocrine (36) and exocrine (25) pancreatic function. Almost all patients returned to full or only slightly impaired activity, were free of pain or had less pain and weight increase. Exocrine pancreatic function (secretin-pancreozymin test and faecal fat) was noted in 11 of 25 patients. In another 11 pre-operative progression was arrested. But endocrine function improved in only three of 36 and worsened in 13 (manifestation of subclinical diabetes in eight, worse glucose tolerance in five). The results justify a more active surgical approach in the treatment of chronic pancreatitis in order to save the patients from an often long and painful "burning out" of the disease on purely conservative treatment. Furthermore, exocrine pancreatic function, at least, is maintained or improved.

Topics: Adolescent; Adult; Body Weight; Cholecystokinin; Chronic Disease; Diabetes Complications; Feces; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Lipids; Male; Middle Aged; Pancreatitis; Secretin

Idiopathic late-onset immunoglobulin deficiency in a young man was associated with achlorhydria and a severe intestinal malabsorption syndrome that did not respond to conventional therapy. Combined therapy with high doses of prednisone and tetracycline hydrochloride resulted in weight gain, cessation of diarrhea, improved absorption of water, fat, and vitamin B12, and production of gastric acid after stimulation with histamine. Serum immunoglobulin levels, however, did not increase.

Topics: Achlorhydria; Adult; Age Factors; Body Weight; Celiac Disease; Cholecystokinin; Diarrhea; Drug Therapy, Combination; Humans; Immunoglobulin M; Immunologic Deficiency Syndromes; Malabsorption Syndromes; Male; Prednisone; Tetracycline; Vitamin B 12

Topics: Age Factors; Body Height; Body Weight; Child; Cholecystokinin; Cystic Fibrosis; Female; Humans; Infant; Male; Pancreas; Pancreatic Diseases; Secretin

Topics: Amylases; Animals; Body Weight; Cholecystokinin; Diet; Dose-Response Relationship, Drug; Glycine max; Male; Pancreas; Rats; Secretin; Stimulation, Chemical; Time Factors; Trypsin

Topics: Aged; Bicarbonates; Body Weight; Cholecystokinin; Eczema; Erythema; Female; Humans; Pancreatic Neoplasms; Secretin; Syringomyelia

Topics: Adult; Amino Acids; Amylases; Bile Acids and Salts; Body Weight; Caseins; Cholecystokinin; Cholesterol; Diet; Dietary Carbohydrates; Dietary Proteins; Female; Humans; Intubation, Gastrointestinal; Lipase; Male; Minerals; Nutritional Physiological Phenomena; Perfusion; Protein Hydrolysates; Time Factors; Triglycerides; Trypsin; Vitamins

Topics: Amylases; Animals; Bicarbonates; Body Weight; Cholecystokinin; Dietary Fats; Duodenum; Fatty Acids, Nonesterified; Feces; Gastric Juice; Intestinal Secretions; Lipids; Male; Pancreas; Pancreatectomy; Pancreatic Juice; Rats; Rats, Inbred Strains; Secretin; Time Factors; Triglycerides; Trypsin

Topics: Animals; Bile; Biliary Fistula; Body Weight; Cholecystectomy; Cholecystokinin; Common Bile Duct; Dogs; Dose-Response Relationship, Drug; Fasting; Food; Infusions, Parenteral; Liver; Stimulation, Chemical; Time Factors

Topics: Animals; Atrophy; Body Weight; Castration; Cholecystokinin; Chymotrypsin; Female; Fishes; Fresh Water; Intestines; Male; Microscopy; Organ Size; Ovary; Staining and Labeling; Testis; Time Factors; Trypsin

Topics: Amylases; Animal Nutritional Physiological Phenomena; Animals; Body Weight; Cholecystokinin; Diet; Flour; Glycine max; Hot Temperature; Male; Pancreas; Rats; Secretory Rate; Stimulation, Chemical; Trypsin Inhibitors

Topics: Adolescent; Bile Acids and Salts; Bile Ducts; Bile Ducts, Intrahepatic; Body Weight; Celiac Disease; Child; Child, Preschool; Cholecystokinin; Cholestyramine Resin; Chronic Disease; Diet Therapy; Dietary Fats; Duodenum; Female; Humans; Infant; Intestinal Secretions; Liver Cirrhosis; Liver Diseases; Liver Function Tests; Male; Triglycerides

Topics: Amylases; Animals; Body Weight; Chickens; Cholecystokinin; Dietary Proteins; Fasting; Gallbladder; Glycine max; Male; Organ Size; Pancreas; Proteins; Trypsin Inhibitors

Topics: Animal Nutritional Physiological Phenomena; Animals; Blood Glucose; Body Weight; Cholecystokinin; Feces; Glucose Tolerance Test; Insulin; Insulin Secretion; Islets of Langerhans; Male; Organ Size; Pancreas; Pancreatic Ducts; Rats; Secretin

Topics: Animals; Body Weight; Chickens; Chlorides; Cholecystokinin; Gastric Fistula; Gastric Juice; Hydrogen-Ion Concentration; Injections, Subcutaneous; Kinetics; Pepsin A; Potassium; Secretory Rate; Sodium; Stomach, Avian; Time Factors

Topics: Bile; Bile Acids and Salts; Body Weight; Cholecystokinin; Cholelithiasis; Cholesterol; Cholestyramine Resin; Chromatography, Gas; Clofibrate; Female; Gallbladder; Humans; Phosphatidylcholines

Topics: Adult; Bile; Bile Acids and Salts; Body Weight; Cholecystokinin; Cholesterol; Dietary Fats; Duodenum; Egg Yolk; Female; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Phosphorus; Proteins; Solubility; Time Factors

Topics: Adult; Bile; Bile Acids and Salts; Body Weight; Cholecystokinin; Cholesterol; Cholestyramine Resin; Duodenum; Female; Glycine; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Male; Phosphorus; Solubility; Taurine; Time Factors

Topics: Bicarbonates; Bile Pigments; Body Weight; Celiac Disease; Chlorides; Cholecystokinin; Duodenal Ulcer; Duodenum; Humans; Hydrochloric Acid; Intestinal Secretions; Jejunum; Secretin; Trypsin

Topics: Adult; Amylases; Body Weight; Cholecystokinin; Fasting; Humans; Lipase; Male; Pancreas; Pancreatic Juice; Peptide Hydrolases; Secretin; Time Factors

Topics: Adult; Aged; Amylases; Bicarbonates; Bilirubin; Body Surface Area; Body Weight; Cholecystokinin; Clinical Enzyme Tests; Duodenum; Fasting; Female; Humans; Lipase; Male; Middle Aged; Pancreas; Secretin; Stimulation, Chemical

Topics: Adolescent; Age Factors; Amylases; Bicarbonates; Body Weight; Child; Child, Preschool; Cholecystokinin; Cystic Fibrosis; Duodenum; Exocrine Glands; Humans; Infant; Intubation, Gastrointestinal; Pancreas; Pancreatic Diseases; Pancreatic Juice; Secretin; Water

Topics: Acetazolamide; Animals; Body Weight; Cats; Cholecystokinin; Dogs; Exocrine Glands; Furosemide; Gastrins; Humans; Neostigmine; Pancreatic Juice; Rats; Scopolamine; Serotonin

The rates of fluid transfer across human gallbladders obtained at cholecystectomy for cholelithiasis were determined by the measurement of weight changes of everted preparations under controlled conditions. Active transport of fluid from the mucosal to the serosal surface was indicated since weight gain occurred with the same solution on both sides of the membrane and against hydrostatic, osmotic, and potential differences. With respect to sodium, the fluid transferred was isotonic to the bathing solutions. Metabolic inhibitors and temperature extremes inhibited weight gain. In addition, muscle contractions in this in vitro preparation were related to the rates and direction of fluid movement. Cholecystokinin increased muscle activity and caused weight loss in preparations that previously had gained weight. Norepinephrine caused weight gain or increased weight gain in all preparations tested. The direction of net fluid movement in the isolated everted human gallbladder was determined by the opposing forces of active mucosal transport and a filtration pressure generated by muscle contractions.

Topics: Biological Transport, Active; Body Weight; Chemical Phenomena; Chemistry, Physical; Chlorides; Cholecystokinin; Electrophysiology; Gallbladder; Humans; Membrane Potentials; Mucous Membrane; Muscle Contraction; Norepinephrine; Osmosis; Potassium; Serous Membrane; Sodium; Temperature; Water-Electrolyte Balance

Topics: Amylases; Animals; Body Weight; Cholecystokinin; Enzyme Precursors; Female; Male; Methacholine Compounds; Organ Size; Pancreas; Parotid Gland; Rats; Secretin; Submandibular Gland; Trypsinogen