oxytocin and Weight-Loss

The neuropeptide oxytocin (OT) has emerged as an important anorexigen in the regulation of food intake and energy balance. It has been shown that the release of OT and activation of hypothalamic OT neurons coincide with food ingestion. Its effects on feeding have largely been attributed to limiting meal size through interactions in key regulatory brain regions governing the homeostatic control of food intake such as the hypothalamus and hindbrain in addition to key feeding reward areas such as the nucleus accumbens and ventral tegmental area. Furthermore, the magnitude of an anorexigenic response to OT and feeding-related activation of the brain OT circuit are modified by the composition and flavor of a diet, as well as by a social context in which a meal is consumed. OT is particularly effective in reducing consumption of carbohydrates and sweet tastants. Pharmacologic, genetic, and pair-feeding studies indicate that OT-elicited weight loss cannot be fully explained by reductions of food intake and that the overall impact of OT on energy balance is also partly a result of OT-elicited changes in lipolysis, energy expenditure, and glucose regulation. Peripheral administration of OT mimics many of its effects when it is given into the central nervous system, raising the questions of whether and to what extent circulating OT acts through peripheral OT receptors to regulate energy balance. Although OT has been found to elicit weight loss in female mice, recent studies have indicated that sex and estrous cycle may impact oxytocinergic modulation of food intake. Despite the overall promising basic research data, attempts to use OT in the clinical setting to combat obesity and overeating have generated somewhat mixed results. The focus of this mini-review is to briefly summarize the role of OT in feeding and metabolism, address gaps and inconsistencies in our knowledge, and discuss some of the limitations to the potential use of chronic OT that should help guide future research on OT as a tailor-made anti-obesity therapeutic.

Topics: Animals; Carbohydrates; Eating; Female; Glucose; Mice; Obesity; Oxytocin; Receptors, Oxytocin; Weight Loss

There is growing evidence that oxytocin (OXT), a hypothalamic hormone well recognized for its effects in inducing parturition and lactation, has important metabolic effects in both sexes. The purpose of this review is to summarize the physiologic effects of OXT on metabolism and to explore its therapeutic potential for metabolic disorders. In model systems, OXT promotes weight loss by decreasing energy intake. Pair-feeding studies suggest that OXT-induced weight loss may also be partly due to increased energy expenditure and/or lipolysis. In humans, OXT appears to modulate both homeostatic and reward-driven food intake, although the observed response depends on nutrient milieu (eg, obese vs. nonobese), clinical characteristics (eg, sex), and experimental paradigm. In animal models, OXT is anabolic to muscle and bone, which is consistent with OXT-induced weight loss occurring primarily via fat loss. In some human observational studies, circulating OXT concentrations are also positively associated with lean mass and bone mineral density. The impact of exogenous OXT on human obesity is the focus of ongoing investigation. Future randomized, placebo-controlled clinical trials in humans should include rigorous, standardized, and detailed assessments of adherence, adverse effects, pharmacokinetics/pharmacodynamics, and efficacy in the diverse populations that may benefit from OXT, in particular those in whom hypothalamic OXT signaling may be abnormal or impaired (eg, individuals with Sim1 deficiency, Prader-Willi syndrome, or craniopharyngioma). Future studies will also have the opportunity to investigate the characteristics of new OXT mimetic peptides and the obligation to consider long-term effects, especially when OXT is given to children and adolescents. (Endocrine Reviews XX: XX - XX, 2020).

Topics: Animals; Body Composition; Bone Density; Eating; Humans; Obesity; Oxytocin; Weight Loss

Oxytocin, a hypothalamic hormone that is secreted directly into the brain and enters the peripheral circulation through the posterior pituitary gland, regulates a range of physiologic processes, including eating behaviour and metabolism. In rodents and nonhuman primates, chronic oxytocin administration leads to sustained weight reduction by reducing food intake, increasing energy expenditure and inducing lipolysis. Oxytocin might improve glucose homeostasis, independently of its effects on weight. Clinical studies are beginning to translate these important preclinical findings to humans. This Review describes key data linking oxytocin to eating behaviour and metabolism in humans. For example, a single intranasal dose of oxytocin can reduce caloric intake, increase fat oxidation and improve insulin sensitivity in men. Furthermore, a pilot study of 8 weeks of oxytocin treatment in adults with obesity or overweight led to substantial weight loss. Together, these data support further investigation of interventions that target pathways involving oxytocin as potential therapeutics in metabolic disorders, including obesity and diabetes mellitus. Therapeutic considerations and areas for further research are also discussed.

Topics: Adult; Animals; Dietary Fats; Energy Intake; Energy Metabolism; Feeding Behavior; Female; Glucose; Humans; Insulin Resistance; Lipolysis; Male; Metabolism; Obesity; Overweight; Oxidation-Reduction; Oxytocin; Pilot Projects; Weight Loss

Obesity and its associated metabolic disorders are growing health concerns in the US and worldwide. In the US alone, more than two-thirds of the adult population is classified as either overweight or obese [1], highlighting the need to develop new, effective treatments for these conditions. Whereas the hormone oxytocin is well known for its peripheral effects on uterine contraction during parturition and milk ejection during lactation, release of oxytocin from somatodendrites and axonal terminals within the central nervous system (CNS) is implicated in both the formation of prosocial behaviors and in the control of energy balance. Recent findings demonstrate that chronic administration of oxytocin reduces food intake and body weight in diet-induced obese (DIO) and genetically obese rodents with impaired or defective leptin signaling. Importantly, chronic systemic administration of oxytocin out to 6 weeks recapitulates the effects of central administration on body weight loss in DIO rodents at doses that do not result in the development of tolerance. Furthermore, these effects are coupled with induction of Fos (a marker of neuronal activation) in hindbrain areas (e.g. dorsal vagal complex (DVC)) linked to the control of meal size and forebrain areas (e.g. hypothalamus, amygdala) linked to the regulation of food intake and body weight. This review assesses the potential central and peripheral targets by which oxytocin may inhibit body weight gain, its regulation by anorexigenic and orexigenic signals, and its potential use as a therapy that can circumvent leptin resistance and reverse the behavioral and metabolic abnormalities associated with DIO and genetically obese models.

Topics: Adult; Animals; Appetite Depressants; Appetite Regulation; Body Weight; Energy Metabolism; Humans; Oxytocin; Signal Transduction; Weight Loss

Obesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed. Oxytocin administration induces weight loss in animal models of obesity via effects on caloric intake, energy expenditure, and fat metabolism. We study intranasal oxytocin, an investigational drug shown to reduce caloric intake in humans, as a potential novel treatment for obesity.. We report the rationale, design, methods, and biostatistical analysis plan of a randomized, double-blind, placebo-controlled clinical trial of intranasal oxytocin for weight loss (primary endpoint) in adults with obesity. Participants (aged 18-45 years) were randomly allocated (1:1) to oxytocin (four times daily over eight weeks) versus placebo. Randomization was stratified by biological sex and BMI (30 to <35, 35 to <40, ≥40 kg/m. Sixty-one male and female participants aged 18-45 years were randomized (mean age 34 years, mean BMI 37 kg/m. Investigating intranasal oxytocin's efficacy, safety, and mechanisms as an anti-obesity medication will advance the search for optimal treatment strategies for obesity and its associated severe sequelae.

Topics: Administration, Intranasal; Adult; Animals; Double-Blind Method; Female; Humans; Male; Middle Aged; Obesity; Oxytocin; Treatment Outcome; Weight Loss

Previous studies indicate that oxytocin (OT) administration reduces body weight in high-fat diet (HFD)-induced obese (DIO) rodents through both reductions in food intake and increases in energy expenditure. We recently demonstrated that chronic hindbrain [fourth ventricular (4V)] infusions of OT evoke weight loss in DIO rats. Based on these findings, we hypothesized that chronic 4V OT would elicit weight loss in DIO mice. We assessed the effects of 4V infusions of OT (16 nmol/day) or vehicle over 28 days on body weight, food intake, and body composition. OT reduced body weight by approximately 4.5% ± 1.4% in DIO mice relative to OT pretreatment body weight (

Topics: Adipocytes, Brown; Adipocytes, White; Adiposity; Animals; Anti-Obesity Agents; Diet, High-Fat; Disease Models, Animal; Eating; Energy Intake; Infusions, Intraventricular; Leptin; Male; Mice, Inbred C57BL; Obesity; Oxytocin; Rhombencephalon; Thermogenesis; Uncoupling Protein 1; Weight Loss

Oxytocin (OT) administration elicits weight loss in diet-induced obese (DIO) rodents, nonhuman primates, and humans by reducing energy intake and increasing energy expenditure. Although the neurocircuitry underlying these effects remains uncertain, OT neurons in the paraventricular nucleus are positioned to control both energy intake and sympathetic nervous system outflow to interscapular brown adipose tissue (BAT) through projections to the hindbrain nucleus of the solitary tract and spinal cord. The current work was undertaken to examine whether central OT increases BAT thermogenesis, whether this effect involves hindbrain OT receptors (OTRs), and whether such effects are associated with sustained weight loss following chronic administration. To assess OT-elicited changes in BAT thermogenesis, we measured the effects of intracerebroventricular administration of OT on interscapular BAT temperature in rats and mice. Because fourth ventricular (4V) infusion targets hindbrain OTRs, whereas third ventricular (3V) administration targets both forebrain and hindbrain OTRs, we compared responses to OT following chronic 3V infusion in DIO rats and mice and chronic 4V infusion in DIO rats. We report that chronic 4V infusion of OT into two distinct rat models recapitulates the effects of 3V OT to ameliorate DIO by reducing fat mass. While reduced food intake contributes to this effect, our finding that 4V OT also increases BAT thermogenesis suggests that increased energy expenditure may contribute as well. Collectively, these findings support the hypothesis that, in DIO rats, OT action in the hindbrain evokes sustained weight loss by reducing energy intake and increasing BAT thermogenesis.

Topics: Adipose Tissue, Brown; Animals; Appetite Depressants; Diet, High-Fat; Dose-Response Relationship, Drug; Infusions, Intraventricular; Male; Mice; Mice, Inbred C57BL; Obesity; Oxytocin; Rats; Rats, Long-Evans; Rats, Sprague-Dawley; Rhombencephalon; Species Specificity; Thermogenesis; Treatment Outcome; Weight Loss

Gastric electrical stimulation (GES) has great potential for the treatment of obesity. We investigated the impact of chronic GES on the alteration of adipose tissue and the regulation of neuropeptide Y (NPY), orexin (OX), α-melanocyte-stimulating hormone (α-MSH) and oxytocin (OXT), and their receptors in several tissues.. Most of the experiments included three groups of diet-induced obesity rats: (1) sham-GES (SGES); (2) GL-6mA (GES with 6 mA, 4 ms, 40 Hz, 2 s on, 3 s off at lesser curvature); and (3) SGES-PF (SGES rats receiving pair feeding to match the consumption of GL-6mA rats). Chronic GES was applied for 2 h every day for 4 weeks. During treatment with GES, food intake and body weight were monitored weekly. The alteration of epididymal fat weight, gastric emptying, and expression of peptides and their receptors in several tissues were determined.. GL-6mA was more potent than SGES-PF in decreasing body weight gain, epididymal fat tissue weight, adipocyte size and gastric emptying. Chronic GES significantly altered NPY, OX, α-MSH and OXT and their receptors in the hypothalamus, adipose tissue and stomach.. Chronic GES effectively leads to weight loss by reducing food intake, fat tissue weight and gastric emptying. NPY, α-MSH, orexin and OXT, and their receptors in the hypothalamus, adipose tissue and stomach appear to be involved in the anti-obesity effects of chronic GES.

Topics: Adipocytes; alpha-MSH; Animals; Disease Models, Animal; Eating; Electric Stimulation Therapy; Electrodes, Implanted; Epididymis; Gastric Emptying; Gastric Mucosa; Ghrelin; Hypothalamus; Intra-Abdominal Fat; Leptin; Male; Neuropeptide Y; Obesity; Orexin Receptors; Orexins; Oxytocin; Pro-Opiomelanocortin; Rats; Rats, Sprague-Dawley; Receptor, Melanocortin, Type 3; Receptors, G-Protein-Coupled; Receptors, Melanocortin; Receptors, Neuropeptide; Receptors, Neuropeptide Y; Receptors, Oxytocin; RNA, Messenger; Weight Loss

Based largely on a number of short-term administration studies, growing evidence suggests that central oxytocin is important in the regulation of energy balance. The goal of the current work is to determine whether long-term third ventricular (3V) infusion of oxytocin into the central nervous system (CNS) is effective for obesity prevention and/or treatment in rat models. We found that chronic 3V oxytocin infusion between 21 and 26 days by osmotic minipumps both reduced weight gain associated with the progression of high-fat diet (HFD)-induced obesity and elicited a sustained reduction of fat mass with no decrease of lean mass in rats with established diet-induced obesity. We further demonstrated that these chronic oxytocin effects result from 1) maintenance of energy expenditure at preintervention levels despite ongoing weight loss, 2) a reduction in respiratory quotient, consistent with increased fat oxidation, and 3) an enhanced satiety response to cholecystokinin-8 and associated decrease of meal size. These weight-reducing effects persisted for approximately 10 days after termination of 3V oxytocin administration and occurred independently of whether sucrose was added to the HFD. We conclude that long-term 3V administration of oxytocin to rats can both prevent and treat diet-induced obesity.

Topics: Adiposity; Animals; Appetite; Brain; Craving; Diet, High-Fat; Dietary Fats; Infusions, Intraventricular; Lipid Metabolism; Male; Obesity; Oxytocin; Rats; Rats, Sprague-Dawley; Satiety Response; Signal Transduction; Weight Loss

Despite compelling evidence that oxytocin (OT) is effective in reducing body weight (BW) in diet-induced obese (DIO) rodents, studies of the effects of OT in humans and rhesus monkeys have primarily focused on noningestive behaviors. The goal of this study was to translate findings in DIO rodents to a preclinical translational model of DIO. We tested the hypothesis that increased OT signaling would reduce BW in DIO rhesus monkeys by inhibiting food intake and increasing energy expenditure (EE). Male DIO rhesus monkeys from the California National Primate Research Center were adapted to a 12-h fast and maintained on chow and a daily 15% fructose-sweetened beverage. Monkeys received 2× daily subcutaneous vehicle injections over 1 wk. We subsequently identified doses of OT (0.2 and 0.4 mg/kg) that reduced food intake and BW in the absence of nausea or diarrhea. Chronic administration of OT for 4 wk (0.2 mg/kg for 2 wk; 0.4 mg/kg for 2 wk) reduced BW relative to vehicle by 3.3 ± 0.4% (≈0.6 kg; P < 0.05). Moreover, the low dose of OT suppressed 12-h chow intake by 26 ± 7% (P < 0.05). The higher dose of OT reduced 12-h chow intake by 27 ± 5% (P < 0.05) and 8-h fructose-sweetened beverage intake by 18 ± 8% (P < 0.05). OT increased EE during the dark cycle by 14 ± 3% (P < 0.05) and was associated with elevations of free fatty acids and glycerol and reductions in triglycerides suggesting increased lipolysis. Together, these data suggest that OT reduces BW in DIO rhesus monkeys through decreased food intake as well as increased EE and lipolysis.

Topics: Animals; Anti-Obesity Agents; Appetite Depressants; Biomarkers; Dietary Carbohydrates; Disease Models, Animal; Drug Administration Schedule; Eating; Energy Metabolism; Feeding Behavior; Fructose; Injections, Subcutaneous; Lipids; Lipolysis; Macaca mulatta; Male; Obesity; Oxytocin; Time Factors; Weight Loss

Socially monogamous prairie voles (Microtus ochrogaster) are biparental and alloparental. In the present study, we compared behavioral, cardiovascular and neuroendocrine parameters in male prairie voles with experience caring for pups (Fathers), versus reproductively inexperienced Virgin males. Father and Virgins showed generally similar responses to unrelated pups. However, in the Fathers studied prior to and during pup exposure, heart rate was lower and respiratory sinus arrhythmia tended to be higher than that in Virgins. Fathers also displayed comparatively lower levels of anxiety-related behaviors in an open field test. In Fathers, compared to Virgin males, we also found higher levels of oxytocin-immunoreactivity in the paraventricular hypothalamus and two brainstem regions involved in the autonomic regulation of the heart--the nucleus ambiguus and nucleus tractus solitarius. However, Fathers had less oxytocin in the bed nucleus of the stria terminalis. Vasopressin did not differ significantly in these regions. Fathers also weighed less and had less subcutaneous fat and larger testes as a percentage of bodyweight. In conjunction with earlier findings in this species, the present study supports the hypothesis that oxytocin may be involved in the adaptation to fatherhood. These findings also support the hypothesis that males, with or without prior pup experience, may show simultaneous patterns of behavioral nurturance and autonomic states compatible with mobilization and vigilance.

Topics: Adipose Tissue; Animals; Arvicolinae; Brain Stem; Heart Rate; Male; Oxytocin; Paraventricular Hypothalamic Nucleus; Paternal Behavior; Subcutaneous Fat; Testis; Weight Loss

Growing evidence suggests that oxytocin plays an important role in the regulation of energy balance and that central oxytocin administration induces weight loss in diet-induced obese (DIO) animals. To gain a better understanding of how oxytocin mediates these effects, we examined feeding and neuronal responses to oxytocin in animals rendered obese following exposure to either a high-fat (HFD) or low-fat diet (LFD). Our findings demonstrate that peripheral administration of oxytocin dose-dependently reduces food intake and body weight to a similar extent in rats maintained on either diet. Moreover, the effect of oxytocin to induce weight loss remained intact in leptin receptor-deficient Koletsky (fa(k)/fa(k)) rats relative to their lean littermates. To determine whether systemically administered oxytocin activates hindbrain areas that regulate meal size, we measured neuronal c-Fos induction in the nucleus of the solitary tract (NTS) and area postrema (AP). We observed a robust neuronal response to oxytocin in these hindbrain areas that was unexpectedly increased in rats rendered obese on a HFD relative to lean, LFD-fed controls. Finally, we report that repeated daily peripheral administration of oxytocin in DIO animals elicited a sustained reduction of food intake and body weight while preventing the reduction of energy expenditure characteristic of weight-reduced animals. These findings extend recent evidence suggesting that oxytocin circumvents leptin resistance and induces weight-loss in DIO animals through a mechanism involving activation of neurons in the NTS and AP, key hindbrain areas for processing satiety-related inputs.

Topics: Animals; Appetite Depressants; Area Postrema; Combined Modality Therapy; Crosses, Genetic; Dietary Fats; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Leptin; Male; Nerve Tissue Proteins; Neurons; Obesity; Oxytocin; Proto-Oncogene Proteins c-fos; Rats; Rats, Mutant Strains; Rats, Sprague-Dawley; Receptors, Leptin; Recombinant Proteins; Solitary Nucleus; Weight Loss

Gastric electrical stimulation (GES) has been proposed as a therapeutic option for obesity. However, its clinical efficacy is not proven, and its mechanisms remain largely unknown. To compare the peripheral and central neural and behavioral effects in rats of GES with a pulse width currently used in clinical trials (GES-A: 6 mA, 0.3 ms, 40 Hz, 2 s on, 3 s off) and GES with a wider pulse (GES-B: same as GES-A, except that the pulse width is 3 ms). Experiment 1: assessing gastric volume changes as a result of GES. Experiment 2: recording the extracellular potentials of a single neuron in the paraventricular nucleus (PVN) with GES. Experiment 3: determining the effects of GES on oxytocin-immunoreactive (OT-IR) neuron expression in the hypothalamus. Experiment 4: determining the effects of GES on food intake and body weight. GES-B, but not GES-A, significantly increased gastric volume. GES-B activated a higher percentage of gastric distention-responsive neurons in the PVN (93% vs. 81%, P = 0.021) and elicited more intensive neuronal responses than GES-A. The number of OT-IR neurons was significantly increased in the PVN and supraoptic nucleus with both methods of GES compared with control groups. The increase in OT-IR neurons in the PVN was higher with GES-B than with GES-A. A 1-week GES treatment significantly reduced daily food intake and body weight. GES-B was more potent than GES-A in producing weight loss (P < 0.001). The effects of GES depend on the stimulation pulse width. GES with a wider pulse is more effective both peripherally and centrally and more potent in reducing body weight in rats.

Topics: Animals; Disease Models, Animal; Eating; Electric Stimulation Therapy; Equipment and Supplies; Female; Male; Neurons; Obesity; Oligopeptides; Oxytocin; Paraventricular Hypothalamic Nucleus; Pyrrolidonecarboxylic Acid; Rats; Rats, Sprague-Dawley; Stomach; Weight Loss

1. This study presents a time course analysis of the messenger RNA (mRNA) levels of c-fos, vasopressin (VP), and oxytocin (OT) in the paraventricular (PVN) and supraoptic nucleus (SON), following acute and chronic dehydration by water deprivation. 2. Male Wistar rats were separated into five groups: nondehydrated (control group) and dehydrated for 6, 24, 48 and 72 h. Following water deprivation, animals were decapitated, their blood was collected for hematocrit, osmolality, and plasma sodium measurements, and brains were removed for dissection of both PVN and SON. 3. As expected, the hematocrit, osmolality, plasma sodium, and weight loss were increased after water deprivation. In SON, a significant increase in both VP and OT mRNA expression was observed 6 h after dehydration reaching a peak at 24 h and returning to basal levels of expression at 72 h. In the PVN, an increase in both VP and OTmRNA expression occurred 24 h after dehydration. At 72 h the VP and OT mRNA expression levels had decreased but they were still at higher levels than those detected in control animals. 4. These results suggest that SON is the first nucleus to respond to the dehydration stimulus. Additionally, we also observed an increase in c-fos mRNA expression in both PVN and SON 6 h after water deprivation, which progressively decreased 24, 48, and 72 h after the onset of water deprivation. Therefore, it is possible that c-fos may be involved in the modulation of VP and OT genes, regulating the mRNA expression levels on a temporally distinct basis within the PVN and SON.

Topics: Animals; Dehydration; Gene Expression; Hematocrit; Hypothalamus, Anterior; Male; Osmolar Concentration; Oxytocin; Paraventricular Hypothalamic Nucleus; Proto-Oncogene Proteins c-fos; Rats; Rats, Wistar; RNA, Messenger; Sodium; Vasopressins; Water Deprivation; Weight Loss

Mammals respond to electrolyte and water imbalance by a variety of neural and endocrine mechanisms that regulate water and salt intake and loss. We used the expression of c-fos and Fos-related antigens to indicate neuronal activation in hypothalamic neurons of members of an outbred laboratory population of white-footed mice (Peromyscus leucopus) deprived of water for biologically reasonable periods of time (6-18 h). We examined Fos-like immunoreactivity (Fos-LIR) in the supraoptic nucleus (SON) and paraventricular nucleus (PVN). During the dark period, when these animals are normally active, 6 h of water deprivation produced near-maximal increases in the number of cells positive for Fos-LIR in the SON and PVN. In contrast, during the light period, when these mice are normally inactive and do not have access to water, 6 h of water deprivation only slightly affected Fos-LIR. During the day, it required as much as 12 h of water deprivation to produce increases in Fos-LIR cells approaching those achieved at night. Plasma osmolarity was directly related to the number of Fos-LIR cells. In addition, mice lost weight more rapidly at night than during the day when water-deprived, and also recovered that lost weight more rapidly when access to water was returned. Our results show (1) that biologically reasonable levels of water restriction (and resulting changes in blood osmolarity) induce changes in Fos-LIR in this wild mouse species, and (2) that these mice have a daily cycle of sensitivity to water deprivation that is demonstrated by both behavioral, psychological and immunohistological assessment of reactions to water deprivation.

Topics: Analysis of Variance; Animals; Arginine Vasopressin; Circadian Rhythm; Female; Hypothalamus; Immunoenzyme Techniques; Male; Nerve Tissue Proteins; Neurons; Neurosecretory Systems; Osmolar Concentration; Oxytocin; Peromyscus; Proto-Oncogene Proteins c-fos; Time Factors; Water Deprivation; Weight Loss

Oxytocin, vasopressin and corticotrophin releasing factor have anorectic properties when injected centrally. We studied the kinetics of these neuropeptides by injecting fenfluramine, a drug which reduces food intake, in Long Evans rats. The drug was injected daily through a double chronic cannula implanted above the paraventricular nucleus of the hypothalamus; the rats had free access to pure macronutrients. The rats lost weight during the treatment. Their total caloric intake decreased mostly because the carbohydrate intake decreased, while the protein intake increased slightly. The synthesis and release of brain oxytocin and vasopressin were increased and the release of corticotrophin releasing factor was stimulated. The neuropeptides could be involved in fenfluramine-triggered mechanisms.

Topics: Animals; Appetite Depressants; Blood Glucose; Corticotropin-Releasing Hormone; Eating; Fenfluramine; Hypothalamus; Injections; Kinetics; Male; Neuropeptides; Oxytocin; Paraventricular Hypothalamic Nucleus; Rats; Vasopressins; Weight Loss

Impaired glucose tolerance and hyperinsulinaemia are common features of obesity. Since oxytocin has been shown to influence glucose metabolism and insulin secretion, the objective of the present study was to investigate whether the plasma level of oxytocin is elevated in obese subjects and if so, whether it is affected by weight reduction following gastric banding. Repeated blood samples were collected in connection with ingestion of a liquid test meal from subjects weighing about 130 kg. Normal weight subjects were tested likewise. Further tests were performed on obese subjects 6 months after operation with gastric banding and a subsequent weight reduction of about 30 kg. Plasma levels of oxytocin were measured by radioimmunoassay. It was found that plasma levels of oxytocin were 4-fold higher in the obese subjects when compared to the control subjects. Analysis with high performance liquid chromatography demonstrated that the oxytocin-like material, as determined by radioimmunoassay, in extracted plasma from one obese subject coeluted with synthetic oxytocin standard. Ingestion of a test meal did not seem to influence oxytocin levels. The mean oxytocin level was equally elevated in male and female obese subjects. Following operation oxytocin levels decreased significantly, but were still significantly higher than in the control subjects. The mechanism behind the hyperoxytocinaemia and possible consequence of it remain obscure.

Topics: Female; Gastroplasty; Humans; Male; Obesity, Morbid; Oxytocin; Radioimmunoassay; Weight Loss

The development of jaundice was investigated in 275 consecutive full-term infants and determined longitudinally in each neonate. The mean peak of bilirubin was 7.90 +/- 0.20 mg/dl observed at 64.0 +/- 1.3 h of life. Three factors were found to significantly alter the course of hyperbilirubinemia: first and second bilirubin determinations (at 2 to 4 h and 12 to 24 h, respectively), weight loss and male sex. Increased weight loss was positively correlated with hyperbilirubinemia irrespective of the mode of feeding.

Topics: Bilirubin; Breast Feeding; Humans; Infant, Newborn; Longitudinal Studies; Oxytocin; Prospective Studies; Sex Factors; Weight Loss