beta-endorphin and Obesity

We are currently in the midst of a global opioid epidemic. Opioids affect many physiological processes, but one side effect that is not often taken into consideration is the opioid-induced alteration in blood glucose levels.. This review shows that the vast majority of studies report that opioid stimulation increases blood glucose levels. In addition, plasma levels of the endogenous opioid β-endorphin rise in response to low blood glucose. In contrast, in hyperglycaemic baseline conditions such as in patients with type 2 diabetes mellitus (T2DM), opioid stimulation lowers blood glucose levels. Furthermore, obesity itself alters sensitivity to opioids, changes opioid receptor expression and increases plasma β-endorphin levels. Thus, opioid stimulation can have various side effects on glycaemia that should be taken into consideration upon prescribing opioid-based medication, and more research is needed to unravel the interaction between obesity, glycaemia and opioid use.

Topics: Analgesics, Opioid; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Type 2; Epidemics; Humans; Obesity

The polycystic ovary syndrome (PCOS) is a condition characterized by hyperandrogenism and chronic oligo-anovulation. However, many features of the metabolic syndrome are inconsistently present in the majority of women with PCOS. Approximately 50% of PCOS women are overweight or obese and most of them have the abdominal phenotype. Obesity may play a pathogenetic role in the development of the syndrome in susceptible individuals. In fact, insulin possesses true gonadotrophic function and an increased insulin availability at the level of ovarian tissue may favour excess androgen synthesis. Obesity, particularly the abdominal phenotype, may be partly responsible for insulin resistance and associated hyperinsulinemia in women with PCOS. Therefore, obesity-related hyperinsulinemia may play a key role in favouring hyperandrogenism in these women. Other factors such as increased estrogen production rate, increased activity of the opioid system and of the hypothalamic-pituitary-adrenal axis, decreased sex hormone binding globulin synthesis and, possibly, high dietary lipid intake, may be additional mechanisms by which obesity favours the development of hyperandrogenism in PCOS. Irrespective of the pathogenetic mechanism involved, obese PCOS women have more severe hyperandrogenism and related clinical features (such as hirsutism, menstrual abnormalities and anovulation) than normal-weight PCOS women. This picture tends to be more pronounced in obese PCOS women with the abdominal phenotype. Body weight loss is associated with beneficial effects on hormones, metabolism and clinical features. A further clinical and endocrinological improvement can also be achieved by adding insulin-sensitizing agents and/or antiandrogens to weight reduction programmes. These obviously emphasize the role of obesity in the pathophysiology of PCOS.

Topics: Androgens; beta-Endorphin; Body Composition; Diet; Estrogens; Female; Human Growth Hormone; Humans; Insulin; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin; Somatomedins

Topics: alpha-MSH; Animals; beta-Endorphin; Fasting; Gene Expression Regulation; Humans; Hypothalamus; Leptin; Obesity; Pro-Opiomelanocortin; Receptors, Leptin; Receptors, Pituitary Hormone; RNA, Messenger

Topics: Amino Acid Sequence; Animals; Appetite Regulation; beta-Endorphin; Endorphins; Humans; Models, Biological; Molecular Sequence Data; Naloxone; Obesity; Receptors, Opioid; Stress, Psychological

The discovery of several endogenous substances with morphine-like activity (endorphins and enkephalins) which possess potent behavioral effects, interfering with food and water intake, has led to suggest their implications in the pathogenesis of human obesity. This suggestion is mainly based on: 1) the ability of opiate antagonists naloxone and naltrexone to reduce food intake in some particular situations associated with obesity: 2) the existence of raised plasma levels of beta-endorphin in obese children and adults not corrected by weight loss; and 3) the increased responsiveness to the metabolic and hormonal effects of opiate agonism and antagonism found in obese but not in normal weight subjects. Although the problem still awaits a definite answer, it seems not hazardous to hypothesize a role for beta-endorphin in some pathogenetic events associated with human obesity.

Topics: beta-Endorphin; Humans; Obesity

Topics: Appetite; beta-Endorphin; Carbohydrate Metabolism; Humans; Islets of Langerhans; Obesity

Since increased opiate production in obesity has been reported, the effects of naloxone in obese subjects were studied in order to ascertain whether endogenous opioid peptides play a role in the abundant insulin secretion of obesity. The results obtained showed that intravenous administration of naloxone considerably reduced insulin of obese subjects to a mixed meal, whereas it did not modify the blood insulin response to arginine or glucose infusion. Glucagon secretion to ingestion of a mixed meal and to arginine infusion was not modified by the opioid receptor blocking agent. This study seems to indicate that hyperproduction of endogenous opioid peptides in obesity increases insulin secretion stimulated by food intake, whereas it does not appreciably affect insulin production stimulated by circulating glucose or aminoacids.

Topics: Adolescent; Adult; beta-Endorphin; Endorphins; Female; Humans; Insulin; Insulin Secretion; Male; Middle Aged; Naloxone; Obesity

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Blood Pressure; Body Weight; Circadian Rhythm; Female; Humans; Hydrocortisone; Hypertension; Male; Obesity

Of the many factors that influence food intake, there is strong evidence that opioid and CCK peptides, which stimulate feeding and elicit satiety, respectively, are important components that may act in concert to regulate energy balance. Cholecystokinin peptides have been isolated in both the brain and gastrointestinal tract, and changes in concentration in the brain and in plasma have been shown to vary with feeding. Peripherally injected CCK has been shown to elicit satiety in many species, including humans, an effect that may be mediated in the CNS via the vagus. In several species, most notably the sheep, direct injection into the CSF potently decreases food intake. Questions remaining regarding the role of CCK peptides in eliciting satiety include the sites and mechanisms of action. It is unknown whether CCK acts directly on receptors, indirectly on some other parameter, or as a neurotransmitter. Although opioid peptides have also been localized in portions of both the periphery and brain, a specific physiological role for their presence has not yet been determined. Opioid peptides from three families--endorphins, enkephalins, and dynorphins--have been shown to stimulate feeding in various species. They have been active at several opioid receptor types in the CNS, but there is limited evidence to suggest they affect food intake when administered peripherally. In contrast, peripheral injection of opiate antagonists has effectively decreased food intake, an observation that led to the original hypothesis that opioids were involved in the hunger component in the control of food intake and that excess concentrations might be involved in the development of obesity. An increasing body of evidence supports the concept that opioid and CCK peptides may interact to control food intake, but the evidence is more suggestive than conclusive.

Topics: Amino Acid Sequence; Animals; Behavior, Animal; beta-Endorphin; beta-Lipotropin; Brain; Ceruletide; Cholecystokinin; Digestive System Physiological Phenomena; Dynorphins; Eating; Endorphins; Enkephalins; Fasting; Food; Humans; Immunologic Techniques; Kinetics; Morphine; Nervous System; Neurons; Obesity; Peptide Fragments; Protein Precursors; Receptors, Cell Surface; Receptors, Cholecystokinin; Satiation; Sincalide; Species Specificity; Structure-Activity Relationship; Tissue Distribution

Topics: Animals; Appetite Regulation; APUD Cells; beta-Endorphin; Endorphins; Energy Metabolism; Humans; Hunger; Hypothalamo-Hypophyseal System; Mice; Mice, Obese; Nerve Tissue Proteins; Obesity; Pituitary-Adrenal System; Structure-Activity Relationship

There is evidence that endogenous opiates are involved in the control of feeding in experimental animals. Several types of experimental obesity are associated with increased opiate production and/or increased numbers and sensitivity of opiate receptors. Research with experimental animals suggests that nutrients, particularly sugar, have an effect on feeding behavior that is mediated by opiates. For instance, the obesity-producing effect of a palatable diet in rodents is blocked by opiate antagonists. Stress induced feeding in rodents leads to preferential sucrose ingestion and is blocked by opiate antagonists and beta-endorphin. The effect of nutrients on the endogenous opiate system of humans is less clear. Clinical experience suggest that carbohydrates (sugar in particular) play a role in binge eating and obesity. Many binge eaters preferentially eat sweets during a binge. Many obese individuals consume more than half of their total daily calories as carbohydrates. Sweet snacking is a frequent behavior at times of stress. Recent evidence suggests that sugar can lead to increased beta-endorphin production in obese subjects.

Topics: Animals; beta-Endorphin; Diet; Endorphins; Feeding and Eating Disorders; Feeding Behavior; Glucose; Humans; Hyperphagia; Male; Naloxone; Narcotics; Obesity; Time Factors

Topics: Animals; Appetite Regulation; beta-Endorphin; Bombesin; Cholecystokinin; Endorphins; Gastrointestinal Hormones; Mice; Nerve Tissue Proteins; Neurotensin; Obesity; Pancreatic Polypeptide; Peptides; Rats; Somatostatin

Topics: Analgesics; Animals; Appetite Depressants; Appetite Regulation; beta-Endorphin; Dynorphins; Endorphins; Humans; Narcotics; Obesity; Peptides; Stimulation, Chemical

Individual responses to weight loss (WL) medications vary widely and prediction of response remains elusive.. We investigated biomarkers associated with use of lorcaserin (LOR), a 5HT2cR agonist that targets proopiomelanocortin (POMC) neurons that regulate energy and glucose homeostasis, to identify predictors of clinical efficacy.. Thirty individuals with obesity were treated with 7 days of placebo and LOR in a randomized crossover study. Nineteen participants continued on LOR for 6 months. Cerebrospinal fluid (CSF) POMC peptide measurements were used to identify potential biomarkers that predict WL. Insulin, leptin, and food intake during a meal were also studied.. LOR induced a significant decrease in CSF levels of the POMC prohormone and an increase in its processed peptide β-endorphin after 7 days; β-endorphin/POMC increased by 30% (P < .001). This was accompanied by a substantial decrease in insulin, glucose, and homeostasis model assessment of insulin resistance before WL. Changes in CSF POMC peptides persisted after WL (6.9%) at 6 months that were distinct from prior reports after diet alone. Changes in POMC, food intake, or other hormones did not predict WL. However, baseline CSF POMC correlated negatively with WL (P = .07) and a cutoff level of CSF POMC was identified that predicted more than 10% WL.. Our results provide evidence that LOR affects the brain melanocortin system in humans and that effectiveness is increased in individuals with lower melanocortin activity. Furthermore, early changes in CSF POMC parallel WL-independent improvements in glycemic indexes. Thus, assessment of melanocortin activity could provide a way to personalize pharmacotherapy of obesity with 5HT2cR agonists.

Topics: beta-Endorphin; Cross-Over Studies; Glucose; Humans; Insulin; Melanocortins; Obesity; Pro-Opiomelanocortin; Weight Loss

In obesity, metabolic and voluntary factors regulate appetite, and a dysregulation of the reward pathway was demonstrated in all addiction disorders. Deep transcranial magnetic stimulation (dTMS) is already used to modulate cerebral dopamine activation in neuro-psychiatric diseases. We presently assess the acute effect of high frequency (HF) and low frequency (LF) dTMS on the modulation of the main neuropeptides and neurotransmitters involved in the reward pathway in obese subjects.. This study was designed as a double-blind, sham-controlled, randomized clinical trial. Thirty-three obese patients (9 males, 24 females, age 48.1 ± 10.6, BMI 36.4 ± 4.7) were enrolled in the study. All patients were studied during a single dTMS session and blood aliquots were drawn before and after a single dTMS session. Metabolic and neuro-endocrine parameters were evaluated before and after: (1) 18 Hz dTMS (HF, 13 patients); (2) 1 Hz dTMS (LF, 10 patients); (3) Sham treatment (Sham, 10 patients).. No statistically significant variations in metabolic parameters, systolic and diastolic blood pressure, and heart rate were shown acutely. HF showed a significant increase of β-endorphin compared to other groups (p = 0.048); a significant increase of ghrelin in LF (p = 0.041) was also demonstrated.. A single session of HF dTMS treatment determines in obese subjects an acute increase of β-endorphin level, indicating an activation of the reward pathway. The present findings constitute proof of principle for a potential application of this methodology in obesity treatment.

Topics: Adult; beta-Endorphin; Blood Glucose; Blood Pressure; Double-Blind Method; Female; Ghrelin; Heart Rate; Humans; Leptin; Male; Middle Aged; Obesity; Transcranial Magnetic Stimulation

Previously it was shown that a brief yoga-based lifestyle intervention was efficacious in reducing oxidative stress and risk of chronic diseases even in a short duration. The objective of this study was to assess the efficacy of this intervention in reducing stress and inflammation in patients with chronic inflammatory diseases.. This study reports preliminary results from a nonrandomized prospective ongoing study with pre-post design.. The study was conducted at the Integral Health Clinic, an outpatient facility conducting these yoga-based lifestyle intervention programs for prevention and management of chronic diseases.. Patients with chronic inflammatory diseases and overweight/obese subjects were included while physically challenged, and those on other interventions were excluded from the study.. A pretested intervention program included asanas (postures), pranayama (breathing exercises), stress management, group discussions, lectures, and individualized advice.. There was a reduction in stress (plasma cortisol and β-endorphin) and inflammation (interleukin [IL]-6 and tumor necrosis factor [TNF]-α) at day 0 versus day 10.. Eighty-six (86) patients (44 female, 42 male, 40.07 ± 13.91 years) attended this program. Overall, the mean level of cortisol decreased from baseline to day 10 (149.95 ± 46.07, 129.07 ± 33.30 ng/mL; p=0.001) while β-endorphins increased from baseline to day 10 (3.53 ± 0.88, 4.06 ± 0.79 ng/mL; p=0.024). Also, there was reduction from baseline to day 10 in mean levels of IL-6 (2.16 ± 0.42, 1.94 ± 0.10 pg/mL, p=0.036) and TNF-α (2.85 ± 0.59, 1.95 ± 0.32 pg/mL, p=0.002).. This brief yoga-based lifestyle intervention reduced the markers of stress and inflammation as early as 10 days in patients with chronic diseases; however, complete results of this study will confirm whether this program has utility as complementary and alternative therapy.

Topics: Adult; beta-Endorphin; Breathing Exercises; Chronic Disease; Counseling; Female; Group Processes; Health Education; Humans; Hydrocortisone; Inflammation; Interleukin-6; Life Style; Male; Meditation; Middle Aged; Obesity; Relaxation Therapy; Stress, Psychological; Treatment Outcome; Tumor Necrosis Factor-alpha; Yoga

This study aims to investigate the role of changes in leptin and beta endorphin (BE) levels in weight loss following electroacupuncture (EA) application in obesity treatment. EA was applied to 20 females who were 41.45 +/- 4.71 years old and had a body mass index of 36.00 +/- 2.66; and a diet program was applied to 20 females who were 42.30 +/- 4.35 years old and had a body mass index of 34.90 +/- 3.21. There was a 4.5% weight reduction in the patients with EA application, whereas patients on diet restriction had a 3.1% weight reduction. A decrease of loss of body weight was observed in the EA group (p < 0.000) when compared against the diet restricted group. A decrease of serum leptin levels (p < 0.000) and an increase in the serum BE (p < 0.05) levels were observed in the EA group compared to the diet restricted group. In this study, reduced serum leptin levels paralleling to weight loss were observed in the EA group. Furthermore, it is thought that in the EA applied group, increasing serum BE level probably enhanced the lipolitic activity which may have caused weight loss in obese people by mobilizing energy stores. It may be considered that the EA application with diet restriction in obesity treatment is more effective than the diet restriction alone.

Topics: Adult; beta-Endorphin; Body Mass Index; Diet, Reducing; Electroacupuncture; Female; Humans; Leptin; Obesity; Weight Loss

Some neuropeptides and monoaminergic neurotransmitters may affect hypothalamic feeding centres, sympathetic activity and thermogenesis. Sibutramine (BTS54524; N-[1-[1(4-chloro phenyl) cyclobutyl]-3methyl N,N-dimethylamine hydrochloride monohydrate) is a new 5-HT serotonin and noradrenaline reuptake inhibitor (SNRI), antiobesity drug. The aim of this study was to evaluate the effects of the sibutramine therapy on plasma neuropeptide Y (NPY), insulin, leptin and beta-endorphin concentrations in obese patients.. Sibutramine, serotonin and noradrenaline reuptake antiobesity drug was administered for 6 months in a dose of 10 mg daily in 60 obese women (BMI 30-40 kg/m2) (mean 34 kg/m2). Plasma NPY, leptin, beta-endorphin and insulin concentrations were measured with RIA methods using commercial kits (Peninsula Lab, Linco, Peninsula Lab, Swierk respectively). The above neuropeptides levels were evaluated before and after the 6 month sibutramine therapy in 60 obese women as well as in 30 obese women on low caloric diet and in 30 of the control group.. In 85% obese patients a decrease of body weight was found after 6 month therapy with sibutramine. A decrease in total cholesterol, LDL and triglycerides and an increase in HDL were observed after the sibutramine treatment. We have demonstrated that the sibutramine therapy leads to the decrease of plasma NPY, beta-endorphin, insulin and leptin concentrations in obese patients. After low diet therapy we have observed a decrease in plasma leptin levels, however we did not find significant changes in plasma leptin, NPY, beta-endorphin and insulin concentrations.. We suggest that the effects on the disturbed activity of NPY, beta-endorphin, insulin and leptin may be involved in the mechanism of sibutramine action.

Topics: Adolescent; Adrenergic Uptake Inhibitors; Adult; Analysis of Variance; Appetite Depressants; Appetite Regulation; beta-Endorphin; Cyclobutanes; Female; Humans; Insulin; Leptin; Neuropeptide Y; Obesity; Reference Values; Selective Serotonin Reuptake Inhibitors; Statistics, Nonparametric

The adrenal production of the delta 5-androgens, dehydroepiandrosterone (DHEA) and its sulfate ester dehydroepiandrosterone sulfate (DHEAS), declines linearly with aging. The evidence that DHEA or DHEAS administration may alleviate some of the problems related to aging has opened new perspectives for clinical research. The present study aims to investigate the effects of a 6-month DHEA supplementation in early and late postmenopausal women, with normal or overweight body mass index (BMI), on the level of circulating steroids, sex hormone binding globulin (SHBG), beta-endorphin and gonadotropins, and on the adrenal gland response to dexamethasone suppression and adrenocorticotropic hormone (ACTH) stimulation. Early postmenopausal women (50-55 years) both normal weight (BMI 20-24, n = 9) and overweight (BMI 26-30, n = 9) and late postmenopausal women (60-65 years) both of normal weight and overweight, were treated with oral DHEA (50 mg/day). Circulating DHEA, DHEAS, 17-OH pregnenolone, progesterone, 17-OH progesterone, allopregnenolone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, SHBG, cortisol, luteinizing hormone, follicle stimulating hormone and beta-endorphin levels were evaluated monthly and a Kupperman score was performed. The product/precursor ratios of adrenal steroid levels were used to assess the relative activities of the adrenal cortex enzymes. Before and after 3 and 6 months of therapy, each women underwent an ACTH stimulating test (10 micrograms i.v. in bolus) after dexamethasone administration (0.5 mg p.o.) to evaluate the response of cortisol, DHEA, DHEAS, androstenedione, 17-OH pregnenolone, allopregnanolone, progesterone and 17-OH progesterone. The between-group differences observed before treatment disappeared during DHEA administration. Levels of 17-OH pregnenolone remained constant during the 6 months. Levels of DHEA, DHEAS, androstenedione, testosterone and dihydrotestosterone increased progressively from the first month of treatment. Levels of estradiol and estrone significantly increased after the first/second month of treatment. Levels of SHBG significantly decreased from the second month of treatment only in overweight late postmenopausal women, while the other groups showed constant levels. Progesterone levels remained constant in all groups, while 17-OH progesterone levels showed a slight but significant increase in all groups. Allopregnanolone and plasma beta-endorphin levels increased progressively a

Topics: Administration, Oral; Adrenocorticotropic Hormone; Aged; Androgens; beta-Endorphin; Body Mass Index; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Dexamethasone; Estradiol; Estrone; Female; Humans; Middle Aged; Obesity; Postmenopause; Progestins; Sex Hormone-Binding Globulin; Steroids

To establish the possible role of hyperinsulinemia in the elevation of plasma beta-endorphin (beta-EP) levels observed in obese patients after an oral glucose load.. Oral glucose tolerance test (OGTT) and euglycemic-hyperinsulinemic clamp.. Two groups of six (age: 22-39 y, BMI: 30-48 kg/m2) and eight obese men (age: 18-37 y, BMI: 35-45 kg/m2), respectively, and five normal weight healthy men (age: 22-30 y, BMI 22-23 kg/m2).. Glucose, insulin and beta-EP levels at baseline and every 30 min until 180 min during the OGTT; glucose, insulin, C-peptide and beta-EP concentrations at baseline and in steady state condition (i.e. during the last 30 min of insulin infusion) in the euglycemic-hyperinsulinemic clamp studies.. In the six obese patients undergoing the OGTT a significant elevation of beta-EP plasma levels was observed between 60 and 90 min after glucose ingestion. In the clamp studies no significant differences in beta-EP plasma levels, blood glucose and serum insulin were observed between obese and normal weight subjects both at baseline and at steady state. A markedly diminished insulin sensitivity along with a lower inhibition of C-peptide during insulin infusion was observed in obese patients compared to control subjects.. A rise in serum insulin levels unaccompanied by a concomitant increase in blood glucose concentration is unable to elicit a beta-EP response in obese patients.

Topics: Adolescent; Adult; beta-Endorphin; Blood Glucose; C-Peptide; Glucose; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Male; Obesity

In this study, we investigated the hypothesis that increased opioid activity may be involved in the development of hyperinsulinemia in women with obesity and abdominal body fat distribution. Two groups of nine obese body (body mass index [BMI], 30 to 40 kg/m2) women with abdominal (A-ob) (waist to hip ratio [WHR] greater than 0.85) or gluteo-femoral (F-ob) (WHR greater than or equal to 0.80) fat distribution were examined and compared with eight normal-weight controls. Basal beta-endorphin levels were higher in the A-ob group than in the other groups. Each woman underwent two oral glucose tolerance tests (OGTT, 75 g glucose). A bolus of naloxone (0.8 mg) followed by a constant infusion of naloxone (0.04 mg/kg/h) or saline was also administered during the glucose challenge in random order, and blood samples for glucose, insulin, and C-peptide were collected at regular times after glucose administration. No difference was observed in basal or stimulated glucose concentrations between the three groups, nor between the saline or naloxone study. However, basal and stimulated insulin levels were significantly higher in obese women (particularly in the A-ob group) than in controls. Naloxone administration, however, did not significantly modify insulin and C-peptide glucose-stimulated concentrations in controls and in the F-ob group, whereas it significantly reduced (by approximately 47%) insulin levels in the A-ob group. Partial correlation coefficients showed a significant negative correlation between percent variation of glucose-stimulated insulin incremental areas during the naloxone study and the WHR in all women considered together (r = .544, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Abdomen; Adipose Tissue; Adult; beta-Endorphin; C-Peptide; Endorphins; Female; Humans; Insulin; Naloxone; Obesity

A subset of the obese population (25-30%) has been reported to engage in binge eating at least twice weekly (bingers) and to exhibit personality traits and food attitudes similar to those of normoweight bulimic women (bulimics). Tricyclic antidepressants and opiate antagonists effectively suppress binge eating in normoweight bulimics. This 8-wk placebo-controlled, double-blind trial investigated the effect of naltrexone and imipramine on 33 obese bingers and 22 bulimics. Naltrexone (100-150 mg/d) produced a significant reduction in binge duration in bulimics (36 +/- 16%, median +/- SIQR; P = 0.02) whereas imipramine significantly reduced binge duration in obese bingers (88 +/- 31%; P = 0.02). A strong placebo effect was observed in obese bingers and, although a reduction in binge frequency occurred with both naltrexone and imipramine, it was not significantly different from the effect in placebo control subjects. We conclude that naltrexone and imipramine may be useful agents in the treatment of binge eating.

Topics: Adult; beta-Endorphin; Bulimia; Double-Blind Method; Female; Humans; Hyperphagia; Imipramine; Naltrexone; Obesity

The role of alpha 2-adrenoceptor stimulation by clonidine on the secretion of beta-endorphin, ACTH, and cortisol in essential hypertension and obesity was studied in 45 subjects: 15 non-obese hypertensives, 10 obese hypertensives, 11 obese normotensives, and 9 healthy subjects. The circadian rhythm of plasma beta-endorphin, ACTH, and cortisol was determined after placebo and after three days on clonidine 0.45 mg daily. Clonidine lowered the blood pressure and blood ACTH and cortisol levels in all the subjects. A significant decrease in beta-endorphin after clonidine occurred in the healthy subjects. In obese normotensives basal beta-endorphin concentrations were significantly higher than in healthy subjects and did not change after clonidine. In about 50% of non-obese and obese hypertensives a significant increase in beta-endorphin secretion after clonidine was noted (responders). In the subgroup of non-obese hypertensive responders no circadian rhythm of beta-endorphin was observed. The results suggest that adrenergic regulation of beta-endorphin secretion is altered in obesity and in certain patients with essential hypertension.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Circadian Rhythm; Clonidine; Female; Humans; Hydrocortisone; Hypertension; Male; Obesity; Time Factors

Opiates stimulate the growth hormone and prolactin responses to stimuli in non-obese humans. Obese patients, however, show lowered growth hormone and prolactin responses and raised beta-endorphin levels. We therefore investigated the effect of the opiate antagonist naloxone on the stimulated growth hormone and prolactin secretions in a controlled double-blind study in obese patients. All patients received 200 micrograms TRH and 0.5 g/kg b.w. arginine together with 2 mg of naloxone or placebo i.v. in a randomized sequence. The TRH- and arginine-induced increases in prolactin and growth hormone were significantly greater after administration of naloxone (p less than 0.05). Naloxone also produced a significant increase in ACTH, cortisol and beta-endorphin when compared with placebo. TSH, triiodothyronine, thyroxine, insulin, glucagon and blood glucose showed no significant differences between both days of the trial. The effect of naloxone on growth hormone and prolactin secretions in obese humans can thus be regarded as a partial normalization. We therefore conclude that the hypothalamic regulatory disturbance of growth hormone and prolactin secretions in the obese could be caused by raised opiate levels.

Topics: Adrenocorticotropic Hormone; Adult; Arginine; beta-Endorphin; Double-Blind Method; Endorphins; Female; Growth Hormone; Humans; Hydrocortisone; Male; Middle Aged; Naloxone; Obesity; Prolactin; Thyrotropin-Releasing Hormone

The melanocortin neuronal system, which consists of hypothalamic proopiomelanocortin (POMC) and agouti-related protein (AgRP) neurons, is a leptin target that regulates energy balance and metabolism, but studies in humans are limited by a lack of reliable biomarkers to assess brain melanocortin activity. The objective of this study was to measure the POMC prohormone and its processed peptide, β-endorphin (β-EP), in cerebrospinal fluid (CSF) and AgRP in CSF and plasma after calorie restriction to validate their utility as biomarkers of brain melanocortin activity. CSF and plasma were obtained from 10 lean and obese subjects after fasting (40 h) and refeeding (24 h), and from 8 obese subjects before and after 6 wk of dieting (800 kcal/day) to assess changes in neuropeptide and hormone levels. After fasting, plasma leptin decreased to 35%, and AgRP increased to 153% of baseline. During refeeding, AgRP declined as leptin increased; CSF β-EP increased, but POMC did not change. Relative changes in plasma and CSF leptin were blunted in obese subjects. After dieting, plasma and CSF leptin decreased to 46% and 70% of baseline, CSF POMC and β-EP decreased, and plasma AgRP increased. At baseline, AgRP correlated negatively with insulin and homeostasis model assessment (HOMA-IR), and positively with the Matsuda index. Thus, following chronic calorie restriction, POMC and β-EP declined in CSF, whereas acutely, only β-EP changed. Plasma AgRP, however, increased after both acute and chronic calorie restriction. These results support the use of CSF POMC and plasma AgRP as biomarkers of hypothalamic melanocortin activity and provide evidence linking AgRP to insulin sensitivity.

Topics: Adult; Agouti-Related Protein; beta-Endorphin; Brain; Caloric Restriction; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Fasting; Female; Humans; Insulin; Insulin Resistance; Leptin; Male; Melanocortins; Middle Aged; Obesity; Pro-Opiomelanocortin; Radioimmunoassay; Young Adult

Obesity is the result of a long-term positive energy balance in which caloric intake overrides energy expenditure. This anabolic state results from the defective activity of hypothalamic neurons involved in the sensing and response to adiposity. However, it is currently unknown what the earliest obesity-linked hypothalamic defect is and how it orchestrates the energy imbalance present in obesity. Using an outbred model of diet-induced obesity we show that defective regulation of hypothalamic POMC is the earliest marker distinguishing obesity-prone from obesity-resistant mice. The early inhibition of hypothalamic POMC was sufficient to transform obesity-resistant in obesity-prone mice. In addition, the post-prandial change in the blood level of β-endorphin, a POMC-derived peptide, correlates with body mass gain in rodents and humans. Taken together, these results suggest that defective regulation of POMC expression, which leads to a change of β-endorphin levels, is the earliest hypothalamic defect leading to obesity.

Topics: Adolescent; Adult; Animals; beta-Endorphin; Diet; Dietary Fats; Energy Intake; Humans; Hypothalamus; Inflammation; Male; Mice; Mice, Obese; Obesity; Pro-Opiomelanocortin; Rats; Rats, Wistar; Young Adult

Endogenous opioids inhibit nociceptive processing and promote the experience of pleasure. It has been proposed that pain and pleasure lie at opposite ends of an affective spectrum, but the relationship between pain and pleasure and the role of opioids in mediating this relationship has not been tested.. Here, we used obese individuals as a model of a dysfunctional opioid system to assess the role of the endogenous opioid peptide, beta-endorphin, on pain and pleasure sensitivity.. Obese (10M/10F) and age- and gender-matched non-obese (10M/10F) controls were included in the study. Pain sensitivity using threshold, tolerance, and subjective rating assessments and perceived sweet pleasantness using sucrose solutions were assessed in two testing sessions with placebo or the opioid antagonist, naltrexone (0.7 mg/kg body weight). Beta-endorphin levels were assessed in both sessions.. Despite having higher levels of baseline beta-endorphin and altered beta-endorphin-reactivity to naltrexone, obese individuals reported a similar increase in pain and decrease in pleasantness following naltrexone compared to non-obese individuals. Beta-endorphin levels did not correlate with pain or pleasantness in either group, but naltrexone-induced changes in pain and pleasantness were mildly correlated. Moreover, naltrexone-induced changes in pain were related to depression scores, while naltrexone-induced changes in sweet pleasantness were related to anxiety scores, indicating that pain and pleasantness are related, but influenced by different processes.

Topics: Adult; beta-Endorphin; Case-Control Studies; Female; Humans; Male; Naltrexone; Narcotic Antagonists; Obesity; Opioid Peptides; Pain Threshold; Pleasure; Sensory Thresholds

Studies implicate opioid transmission in hedonic and metabolic control of feeding, although roles for specific endogenous opioid peptides have barely been addressed. Here, we studied palatable liquid consumption in proenkephalin knockout (PENK KO) and β-endorphin-deficient (BEND KO) mice, and how the body weight of these mice changed during consumption of an energy-dense highly palatable 'cafeteria diet'. When given access to sucrose solution, PENK KOs exhibited fewer bouts of licking than wild types, even though the length of bouts was similar to that of wild types, a pattern that suggests diminished food motivation. Conversely, BEND KOs did not differ from wild types in the number of licking bouts, even though these bouts were shorter in length, suggesting that they experienced the sucrose as being less palatable. In addition, licking responses in BEND, but not PENK, KO mice were insensitive to shifts in sucrose concentration or hunger. PENK, but not BEND, KOs exhibited lower baseline body weights compared with wild types on chow diet and attenuated weight gain when fed cafeteria diet. Based on this and related findings, we suggest endogenous enkephalins primarily set a background motivational tone regulating feeding behavior, whereas β-endorphin underlies orosensory reward in high need states or when the stimulus is especially valuable. Overall, these studies emphasize complex interplays between endogenous opioid peptides targeting μ-receptors, such as enkephalins and endorphins, underlying the regulation of feeding and body weight that might explain the poor efficacy of drugs that generally target μ-opioid receptors in the long-term control of appetite and body weight.

Topics: Animals; Appetite; beta-Endorphin; Body Weight; Case-Control Studies; Diet; Disease Models, Animal; Dose-Response Relationship, Drug; Drinking Behavior; Enkephalins; Feeding Behavior; Female; Food Deprivation; Male; Mice; Mice, Knockout; Obesity; Protein Precursors; Sucrose

Reduced food intake brings about an adaptive decrease in energy expenditure that contributes to the recidivism of obesity after weight loss. Insulin and leptin inhibit food intake through actions in the central nervous system that are partly mediated by the transcription factor FoxO1. We show that FoxO1 ablation in pro-opiomelanocortin (Pomc)-expressing neurons in mice (here called Pomc-Foxo1(-/-) mice) increases Carboxypeptidase E (Cpe) expression, resulting in selective increases of alpha-melanocyte-stimulating hormone (alpha-Msh) and carboxy-cleaved beta-endorphin, the products of Cpe-dependent processing of Pomc. This neuropeptide profile is associated with decreased food intake and normal energy expenditure in Pomc-Foxo1(-/-) mice. We show that Cpe expression is downregulated by diet-induced obesity and that FoxO1 deletion offsets the decrease, protecting against weight gain. Moreover, moderate Cpe overexpression in the arcuate nucleus phenocopies features of the FoxO1 mutation. The dissociation of food intake from energy expenditure in Pomc-Foxo1(-/-) mice represents a model for therapeutic intervention in obesity and raises the possibility of targeting Cpe to develop weight loss medications.

Topics: alpha-MSH; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Carboxypeptidase H; Eating; Female; Forkhead Box Protein O1; Forkhead Transcription Factors; Hypothalamus; Male; Mice; Mice, Knockout; Neurons; Obesity; Pro-Opiomelanocortin; Signal Transduction

Both obesity and increased endorphin production are associated with an increase in blood pressure. We have previously demonstrated that the acute and chronic central nervous system (CNS) administration of beta-endorphin can increase or decrease blood pressure, respectively. Also high fat (HF) diet-induced obesity is associated with increased hypothalamic mu opioid receptors and increased blood pressure in response to ss-endorphins. In this study we investigated the effect of high fat diet-induced obesity on blood pressure, heart rate, and physical activity as well as determined the effect of mu opioids in unanesthetized rats. Male Wistar rats were implanted with a radiotelemetry transmitter to record cardiovascular dynamics and activity. They were fed either a HF diet (HF; 59% fat by caloric content, soy bean oil) or regular chow (control; 12% fat by caloric content). HF rats had higher body weights and their total caloric intake was greater than controls. The systolic blood pressures (SBP) were greater in the HF-obese rats. After 12-13 weeks the rats were infused chronically with a mu opioid agonist (D)-Ala(2), N-Me-Phe(4), Gly(5)-ol]-ENKEPHALIN (DAMGO) or a mu opioid antagonist ss-funaltrexamine (beta-FNA) via intracerebroventricular cannula. DAMGO increased the SBP and heart rate in controls, but not in HF obese rats. DAMGO did not affect physical activity; beta-FNA decreased SBP and increased HR in controls. We concluded that HF rats consumed more calories, gained more weight, and had higher SBP. However, the responsiveness to the mu-receptor agonist was not higher in the HF rats.

Topics: Animals; beta-Endorphin; Blood Pressure; Body Weight; Consciousness; Dietary Fats; Disease Models, Animal; Follow-Up Studies; Heart Rate; Male; Motor Activity; Neurotransmitter Agents; Obesity; Rats; Rats, Wistar; Receptors, Opioid, mu

The purpose of this brief review is to highlight recent studies from our laboratory and collaborators based on the analysis of novel strains of mutant mice that further our understanding of the complex regulatory roles of proopiomelanocortin (POMC) neurons and POMC peptides in energy homeostasis. Mouse models that are considered include a transgenic strain with expression of enhanced green fluorescent protein in POMC neurons, facilitating analyses of the cell intrinsic membrane and synaptic properties, and two gene knockout strains exhibiting either a selective absence of beta-endorphin production or a complete loss of all POMC peptides from the pituitary gland and nervous system. Together these studies demonstrate the wide variety of hormonal, metabolic, and transsynaptic signals that converge on the arcuate hypothalamic nucleus and nucleus tractus solitarius to regulate the activity of POMC neurons. Both melanocortin peptides and the opioid beta-endorphin processed from POMC mediate the homeostatic and behavioral responses linked to POMC neuronal circuits.

Topics: 5' Flanking Region; Animals; beta-Endorphin; Energy Metabolism; Green Fluorescent Proteins; Homeostasis; Mice; Mice, Knockout; Mice, Transgenic; Neurons; Neuropeptides; Obesity; Pituitary Gland; Pro-Opiomelanocortin; Synapses

Proopiomelanocortin (POMC) neurons in the hypothalamus are direct targets of the adipostatic hormone leptin and contribute to energy homeostasis by integrating peripheral and central information. The melanocortin and beta-endorphin neuropeptides are processed from POMC and putatively coreleased at axon terminals. Melanocortins have been shown by a combination of pharmacological and genetic methods to have inhibitory effects on appetite and body weight. In contrast, pharmacological studies have generally indicated that opioids stimulate food intake. Here we report that male mice engineered to selectively lack beta-endorphin, but that retained normal melanocortin signaling, were hyperphagic and obese. Furthermore, beta-endorphin mutant and wild-type mice had identical orexigenic responses to exogenous opioids and identical anorectic responses to the nonselective opioid antagonist naloxone, implicating an alternative endogenous opioid tone to beta-endorphin that physiologically stimulates feeding. These genetic data indicate that beta-endorphin is required for normal regulation of feeding, but, in contrast to earlier reports suggesting opposing actions of beta-endorphin and melanocortins on appetite, our results suggest a more complementary interaction between the endogenously released POMC-derived peptides in the regulation of energy homeostasis.

Topics: Animals; beta-Endorphin; Eating; Energy Metabolism; Glucose; Homeostasis; Hyperinsulinism; Hyperphagia; Leptin; Male; Mice; Mice, Knockout; Naloxone; Narcotic Antagonists; Neuropeptide Y; Obesity; Reference Values

Obesity and high fat diets are associated with an increased prevalence of diabetes, cardiovascular disease, and hypertension. However, the mechanism(s) linking obesity and high fat diet to these metabolic and cardiovascular disorders are not fully elucidated. Leptin stimulates the formation of pro-opiomelanocortin and its products. The stimulation of the central nervous system (CNS) opioids and their receptors is associated with an increase in cardiovascular dynamics. In this study we hypothesized that obesity changed the CNS opioids and their receptors that could play a role in altered cardiovascular and autonomic nervous regulation in obesity. Male Wistar rats were fed either a high fat (HF) or regular chow (control) diet. After 12 weeks, rats were anesthetized and instrumented to record mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). A blood sample was collected and plasma glucose, insulin, leptin, beta-endorphins were measured. The brains were subsequently processed for immunohistochemistry and in situ hybridization. The HF rats were larger and had a greater percentage of body fat. Leptin and insulin levels were also higher in the HF animals. Basal MAP and RSNA were significantly higher in HF rats. Additionally, immunohistochemistry and in situ hybridization demonstrated that HF rats had increased hypothalamus mu opioid receptors compared to controls. These studies suggest that HF feeding is associated with increased body fat, plasma leptin, insulin, and hypothalamic mu opioid receptors. The increased mu opioid receptors may contribute to the higher MAP and RSNA observed in HF animals.

Topics: Animals; Arteries; beta-Endorphin; Dietary Fats; Food, Formulated; Hypertension; Hypothalamus; Immunohistochemistry; Insulin; Kidney; Leptin; Male; Obesity; Opioid Peptides; Rats; Rats, Wistar; Receptors, Opioid, mu; Sympathetic Nervous System; Vasoconstriction

It has been reported that neuropeptides may play a role in the control of appetite and in the mechanism of hormone release. Neuropeptides such as beta-endorphin, neuropeptide Y (NPY), galanin and leptin may affect hormones release, on the other hand the hormonal status may modulate neuropeptide activity.. The material consisted of 90 obese women, 30 women with Anorexia Nervosa, and 30 healthy, lean women of control group. Plasma beta-endorphin, NPY, leptin, somatostatin and serum pituitary and gonadal hormones concentrations were measured with RIA methods.. We observed the highest plasma NPY levels in obese hypertensive and diabetic patients. After carbohydrate administration (OGTT) a marked increase of insulin, beta-endorphin and NPY was found. The blunted response of GH to GH-RH may be connected with increased somatostatin activity and hyperinsulinemia. The abnormal response of LH to opioid blockade may be a result of disturbed opioid and NPY activities in obese patients. However in patients with anorexia nervosa, plasma leptin and NPY concentrations were low. The disturbances in beta-endorphin release are also observed.. The neuroendocrine disturbances in obesity and in anorexia nervosa are opposite. The feedback mechanism between leptin and NPY is disturbed in both in obesity and in anorexia nervosa. An abnormal activity of neuropeptides may lead to disturbed control of appetite and hormonal dysregulation in eating disorders.

Topics: Adult; Anorexia Nervosa; Appetite; beta-Endorphin; Diabetes Mellitus; Feedback, Physiological; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Hypertension; Leptin; Luteinizing Hormone; Neuropeptide Y; Neuropeptides; Obesity; Somatostatin

The functional loss of both alleles of the human pro-opiomelanocortin (POMC) gene leads to a very rare syndrome of hypoadrenalism, red hair and early-onset obesity. In order to examine whether more subtle genetic variants in POMC might contribute to early-onset obesity, the coding region of the gene was sequenced in 262 Caucasian subjects with a history of severe obesity from childhood. Two children were found to be heterozygous for a missense mutation, R236G, which disrupts the dibasic cleavage site between beta melanocyte-stimulating hormone (beta-MSH) and beta-endorphin. Beta-TC3 cells transfected with the mutant POMC cDNA produced a mutant beta-MSH/beta-endorphin fusion protein. This fusion protein bound to the human melanocortin-4 receptor (hMC4R) with an affinity similar to its natural ligands, but had a markedly reduced ability to activate the receptor. This variant co-segregated with early-onset obesity over three generations in one family and was absent in 412 normal weight UK Caucasian controls. Combining the results in UK Caucasians with a new case-control study in French subjects and three previously published reports, mutations disrupting this processing site were present in 0.88% of subjects with early-onset obesity and 0.22% of normal-weight controls. These results suggest that the R236G mutation may confer an inherited susceptibility to obesity through the production of an aberrant fusion protein that has the capacity to interfere with central melanocortin signalling.

Topics: Adolescent; Adrenal Insufficiency; Animals; beta-Endorphin; beta-MSH; Case-Control Studies; CHO Cells; Cricetinae; Disease Susceptibility; DNA Mutational Analysis; DNA Primers; Female; Hair Color; Humans; Male; Mutation, Missense; Obesity; Pedigree; Peptide Fragments; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Precipitin Tests; Pro-Opiomelanocortin; Receptor, Melanocortin, Type 4; Receptors, Corticotropin; Recombinant Fusion Proteins

The aim of this study was to determine the influence of body weight on circulating plasma levels of beta-endorphin and insulin in women with polycystic ovary disease (PCOD), as well as the correlation between the plasma levels of beta-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with PCOD were recruited, 117 of whom had normal weight (body mass index (BMI) < 25) while 50 were obese (BMI > 25). A venous blood sample was taken and plasma concentrations of beta-endorphin, insulin, gonadotropins, prolactin, progesterone, 17 beta-estradiol, estrone, androgens, dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) were measured. Mean beta-endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese PCOD women than in non-obese ones. Correlation analysis showed a positive association between insulin and beta-endorphin, beta-endorphin and BMI (and weight), insulin and BMI (and weight), and a negative correlation was found between insulin and SHBG. A weak association was found between beta-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma beta-endorphin concentrations correlate more with BMI than with insulinemia.

Topics: Adolescent; Adult; beta-Endorphin; Body Mass Index; Case-Control Studies; Female; Hormones; Humans; Insulin; Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin

Specific binding sites for [125I]beta-endorphin and the delta1-opioid [3H][D-pen(2), D-pen(5)]enkephalin (DPDPE) were quantified using autoradiography in soleus and extensor digitorum longus (EDL) muscles of lean and obese-diabetic (ob/ob) mice. The density of binding was significantly higher in obese-diabetic than lean mice. The uptake of 2-deoxy-D-[1-3H]deoxyglucose, a nonmetabolized glucose analogue, into isolated soleus and EDL muscles was stimulated by beta-endorphin, beta-endorphin 1-27, and DPDPE, but not by the delta2-opioid deltorphin II. Both beta-endorphin and DPDPE stimulated deoxyglucose uptake in obese-diabetic mice. Thus, glucose transport in skeletal muscle may be partly mediated via delta1-opioid receptors. The increased receptor density in obese-diabetic mice may be an adaptive response.

Topics: Animals; Autoradiography; beta-Endorphin; Blood Glucose; Deoxyglucose; Diabetes Mellitus; Enkephalin, D-Penicillamine (2,5)-; Fatty Acids, Nonesterified; Female; Glucose; Insulin; Iodine Radioisotopes; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Muscle, Skeletal; Obesity; Receptors, Opioid, delta; Tritium

In this study, the authors assessed the endocrine system and glucose tolerance in obese and non-obese women chronically treated with typical antipsychotic drugs (AP). In particular, we tested the hypotheses that these subjects display hypogonadism and increased insulin resistance compared to healthy weight-matched controls, as these abnormalities create a tendency towards excessive body weight gain. Twenty-six AP-treated women were matched with 26 healthy women by age, body mass index and day of the menstrual cycle. The following serum variables were evaluated in each subject: glucose tolerance after an oral glucose overload, insulin, leptin, beta-endorphin, reproductive hormones, adrenal steroids and lipids. Compared to controls, AP-treated women displayed significantly higher levels of basal glucose, insulin after 60 min of the glucose overload, prolactin, thyroid stimulating hormone and beta-endorphin, with lower levels of C-Peptide, progesterone, 17-OH progesterone, androstenedione and high-density lipoprotein cholesterol. The levels of estradiol, estrone and leptin did not differ between the groups. Thus, women treated with typical AP appeared to display more insulin resistance than healthy controls, predisposing them to excessive weight gain. Insulin sensitivity might be further impaired when the subject switches to atypical AP administration. Metformin and related agents may reduce body weight in these subjects. The high levels of the opiate beta-endorphin suggest that opiate antagonists such as naloxone and naltrexone might be useful as well. Even though the luteal phase of the menstrual cycle appears to be severely disturbed, the normal serum levels of estradiol and estrone do not support the proposal derived from animal experimental studies about the use of estrogens or tamoxifen to counteract AP-induced obesity.

Topics: Adrenal Glands; Adult; Antipsychotic Agents; beta-Endorphin; Blood Glucose; C-Peptide; Endocrine System; Female; Gonadal Steroid Hormones; Humans; Hypogonadism; Insulin; Insulin Resistance; Leptin; Lipids; Multivariate Analysis; Obesity; Prolactin; Sex Hormone-Binding Globulin; Thyroid Hormones

Effects of obesity on gene expression for opioid peptides and neuropeptide-Y (NPY) in the arcuate nucleus (ARC), and on opioid peptides and alpha-melanocyte stimulating hormone (alpha-MSH) in the paraventricular nucleus (PVN) were examined in obese Zucker rats (18 weeks old). Obese Zucker rats are insulin-resistant, diabetic and hyperleptinemic as indicated by high serum glucose, insulin and leptin levels. ARC proOpiomelanocortin (POMC) mRNA levels were significantly lower in the obese relative to lean Zucker rats and ARC proNeuropeptide Y (proNPY) mRNA levels were higher (P<0.05). There were no differences in proDynorphin and proEnkephalin mRNA levels in the ARC (0.05). Obese Zucker rats had lower alpha-MSH and dynorphin A(1-17) peptide levels in the paraventricular nucleus (PVN) (P<0.05), but did not have lower PVN beta-endorphin peptide levels (0.05). The decrease in POMC in the ARC and decrease in alpha-MSH in the PVN seen in the obese Zucker rat in the present study suggest that reduced activity of the melanocortin system in the ARC to PVN pathway may contribute to the related hyperphagia. Reduced activity of the melanocortin system in the ARC to PVN pathway may be due to a disturbance of leptin signaling coupling to POMC.

Topics: alpha-MSH; Animals; Arcuate Nucleus of Hypothalamus; beta-Endorphin; Blood Glucose; Dynorphins; Energy Metabolism; Enkephalins; Feeding Behavior; Gene Expression; Insulin; Leptin; Male; Melanocytes; Neuropeptide Y; Obesity; Paraventricular Hypothalamic Nucleus; Pro-Opiomelanocortin; Protein Precursors; Rats; Rats, Zucker; RNA, Messenger

Obesity in normal animals has been demonstrated to be associated with a decrease in sensitivity to leptin especially as it relates to leptin's capacity to increase sympathetic nerve activity and enhance cardiovascular dynamics. In normal animals leptin has been demonstrated to exert significant regulatory responses by its capacity to increase proopiomelanocortin (POMC) expression and especially the increase in alpha melanocyte stimulating hormone (alphaMSH). These responses to leptin are blocked by a melanocortin-4 (MC-4) receptor antagonist. In this study we investigated the responsiveness of the sympathetic nervous system and cardiovascular system of high fat fed obese animals to the intracerebroventricular (ICV) administration of the POMC products alphaMSH and beta-endorphin (beta-END). We further investigated these responses in obese animals following leptin administration in the presence of MC-4 receptor and opioid receptor blockade. The ICV administration of leptin resulted in an increase in lumbar sympathetic nerve activity (LSNA) and mean arterial pressure (MAP) in normals but decreased it in the obese. The ICV administration of alphaMSH increased the LSNA and MAP in normal animals but to a lesser degree in obese animals. On the other hand beta-endorphin decreased the LSNA and MAP in normal animals but increased it in obese animals. Additionally ICV leptin administration in obese animals in the presence of MC-4 or opioid receptor blockade resulted in an increase in sympathetic activity and a pressor response. From these studies we conclude that obesity in high fat fed animals is characterized by a decreased sensitivity to alphaMSH and a paradoxical response to beta-endorphin and this altered responsiveness may be a factor in the altered leptin resistance characteristic of obese animals.

Topics: Agouti Signaling Protein; alpha-MSH; Animals; beta-Endorphin; Blood Pressure; Body Weight; Dietary Fats; Drug Resistance; Electrophysiology; Female; Heart Rate; Injections, Intraventricular; Intercellular Signaling Peptides and Proteins; Leptin; Naloxone; Narcotic Antagonists; Obesity; Pressoreceptors; Pro-Opiomelanocortin; Proteins; Rats; Rats, Wistar; Receptor, Melanocortin, Type 4; Receptors, Corticotropin; Receptors, Opioid; Splanchnic Nerves

Complex interactions between the neuroendocrine and the immune systems are present in autoimmune diseases. The central opioid peptide beta-endorphin (BE) has been shown to modulate peripheral immune responses in normal animals. In the present study we analyze the hypothalamic concentrations of this peptide in two models of spontaneous autoimmune disease, the MRL [corrected] lpr/lpr mouse, that develops a lupus-like autoimmune disease, and the obese strain (OS) chickens afflicted with spontaneous autoimmune thyroiditis. In both instances, hypothalamic concentrations of BE are significantly lower than normal controls. In MRL [corrected] lpr/lpr mice, BE is already lower at 1 month of age, when no clinical sign of the disease is yet present. Similarly, low levels of BE are observed in OS chickens before the onset of thyroiditis, i.e., already at the embryonic stage. Moreover, a further decrease of BE is observed in OS chickens in correspondence with the first signs of thyroid mononuclear infiltration. Considering the immunosuppressive effects exerted by central BE, these results are suggestive of the fact that in autoimmune disease prone animals the low hypothalamic concentrations may be one of several factors predisposing for the development of autoimmune disease.

Topics: Animals; Autoimmune Diseases; beta-Endorphin; Chickens; Female; Hypothalamus; Male; Mice; Mice, Inbred MRL lpr; Neuroimmunomodulation; Obesity; Proteinuria; Substance P; Thyroiditis, Autoimmune

Topics: Aging; Animals; Autoimmune Diseases; beta-Endorphin; Chickens; Female; Hypothalamus; Male; Mice; Mice, Inbred MRL lpr; Obesity; Osmolar Concentration; Reference Values

Topics: Alzheimer Disease; beta-Endorphin; beta-Lipotropin; beta-MSH; Diabetes Mellitus; HIV Infections; Humans; Neuropeptides; Obesity; Pituitary Gland; Pro-Opiomelanocortin; Protein Precursors; Serine Endopeptidases

To study the associations of obesity (as body mass index (BMI)), of body fat distribution (as waist to hip ratio (WHR)) and of beta-endorphinaemia (beta-EP-aemia) with fasting insulin and glucose concentrations, with insulin secretion (as first phase insulin response (FPIR)) and with insulin sensitivity (SI) in obese women.. a cross-sectional study of insulin sensitivity in obese women.. 45 obese women (age: 20-70 y, BMI: 27-50).. Frequently sampled intravenous glucose tolerance test (FSIGTT), FPIR, fasting glucose, fasting insulin, BMI, body fat topography (WHR), beta-EP-aemia, plasma ACTH.. In univariate analysis the following positive associations were observed: fasting glucose with age and WHR, fasting insulin with BMI and WHR, beta-EP plasma concentration with WHR; SI was negatively associated with BMI, WHR and beta-EP plasma concentrations. This pattern of associations remained unaltered in multivariate analysis including age, BMI and WHR as independent variables. The contribution of beta-EP plasma concentrations to SI variability was corroborated by a stepwise multiple regression analysis: 53.8% of SI variation could be explained by BMI (30.7%), by beta-EP plasma concentrations (17.2%) and by WHR (5.9%). Finally, women were divided into two groups according to whether they had a peripheral (P-BFD, WHR < or = 0.80, n = 24) or an abdominal (A-BFD, WHR > or = 0.85, n = 16) body fat distribution. After adjustment for age and BMI, SI values were lower while beta-EP and ACTH plasma concentrations were higher in the A-BFD compared to the P-BFD group. In this latter group, 54.8% of SI variation was explained by the same variables as in the whole group. In the A-BFD group, higher WHR was associated with lower FPIR.. 1) The major finding of this study is that, in non-diabetic obese women (especially those with a P-BFD), higher beta-EP plasma concentrations are associated with lower insulin sensitivity. This association is independent of both the magnitude of obesity and the pattern of fat distribution, although these two parameters are strong predictors of SI. 2) The major reduction in SI observed in women with A-BFD probably results from the additive effects of obesity, of elevated beta-EP plasma concentrations and of metabolic and endocrine alterations in relation with the central pattern of fat distribution.

Topics: Adult; Aged; beta-Endorphin; Body Constitution; Cross-Sectional Studies; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Middle Aged; Obesity; Regression Analysis

Beta-endorphin (beta-EP) is a neuropeptide involved in several brain functions, regulating the reproductive axis and behavioral changes. Estrogens play a modulatory role on circulating levels of beta-EP in women. Previous clinical studies have demonstrated high plasma beta-EP levels in obese subjects and increased beta-EP release after an oral glucose tolerance test (OGTT) in normal or obese women. The aim of the present study was to evaluate plasma beta-endorphin levels in response to an OGTT in pre- and postmenopausal obese and non-obese women, in order to investigate if the decrease in gonadal steroid levels at menopause could modify in a different manner the control of beta-endorphin release in response to glucose administration. A group of 24 normal women (age range 45-55 years) were included in the study. The patients were subdivided in four groups of six subjects each: group A, premenopausal women with body mass index (BMI) < 25 (control); group B, premenopausal women with BMI > 25 (obese); group C, post-menopausal women with BMI < 25 (control); group D, postmenopausal women with BMI > 25 (obese). All women were studied between 8.30 and 9.00 am, after overnight fasting, and underwent an OGTT. In obese premenopausal women, basal plasma beta-EP levels were significantly higher than in non-obese women (p < 0.01). In postmenopausal women, regardless of body weight, low basal plasma beta-EP levels were found. A significant increase in plasma beta-EP levels, at 30 and 60 minutes after oral glucose ingestion, was shown in control premenopausal women. No significant modifications to OGTT were shown in plasma beta-EP levels in the other three groups of women. In conclusion, while in premenopausal women the response of plasma beta-EP levels to OGTT is maintained, in postmenopause there is a lack of response to OGTT. This suggests that beta-EP release is dependent upon gonadal steroids, while it is only in part influenced by body weight.

Topics: Adult; beta-Endorphin; Blood Glucose; Body Mass Index; Female; Glucose Tolerance Test; Humans; Insulin; Middle Aged; Obesity; Postmenopause; Premenopause; Radioimmunoassay

To investigate the relationship between plasma beta-endorphin (beta-end) and insulin concentrations and 1) body fat, and 2) nutritional parameters in overweight or obese prepubertal children.. Cross-sectional study on plasma beta-end and insulin concentrations, body fat, indirect parameters of appetite namely daily energy and macronutrient intake.. 143 (67 boys and 76 girls) overweight or obese children (group I) and 48 (27 boys and 21 girls) healthy children with normal parameters of somatic development (group II). Age: 5.8-9.6 y.. Weight, height and subcutaneous skinfold thicknesses, plasma beta-end and insulin concentrations, diet history for energy and macronutrient intake.. Group I was characterised by significantly higher average concentrations of beta-end and insulin in comparison to the control group. The analysis of these concentrations in the subgroups in relation to the percentage of body fat indicates that beta-end concentrations increased more than insulin concentrations with increasing fatness. A significantly positive correlation between beta-end and insulin levels was only noted in group I. Also, only in this group was there a significant positive correlation between beta-end levels and energy and macronutrient intake. In both groups the percentage of energy intake which was fat, correlated positively with beta-end concentrations. Furthermore energy and fat intakes showed a significant positive correlation with insulin levels in both groups.. beta-endorphin and insulin concentrations in overweight and obese prepubertal children are not only higher than in non-obese children but also are positively correlated with each other and with the percentage of body fat. The relationship between plasma beta-end levels and food intake shows that the beta-end level may be able to be used as an indicator of appetite in overweight and obese prepubertal children whose food intake is not restricted.

Topics: Adipose Tissue; Anthropometry; beta-Endorphin; Body Composition; Child; Cohort Studies; Eating; Energy Intake; Female; Humans; Insulin; Male; Obesity

The involvement of the opioid system in human obesity has been demonstrated, but whether the abnormalities in the endorphinergic system play a primary role in overfeeding and weight gain or represent a simple biochemical feature is still unclear. The objectives of this study were to investigate the effects of both physiological and pharmacological plasma beta-endorphin levels on some metabolic and hormonal parameters in a normal weight, but prone to obesity, young population consisting of first degree relatives of obese subjects and in body mass index-, sex, and age- matched control subjects without a family history of obesity. Each subject underwent a 1-h infusion of synthetic human beta-endorphin at a constant rate of 4.5 ng/kg.min (low rate), then after a 1-week interval, at a rate of 500 micrograms/h (high rate). Under basal conditions, there was no significant difference in plasma glucose and pancreatic hormones (insulin, C peptide, and glucagon) between the two groups, except for plasma beta-endorphin levels, which were significantly (P < 0.01) higher in relatives of obese individuals. The low rate of beta-endorphin infusion induced physiological elevations of plasma opioid levels in both groups; no significant change in plasma glucose and pancreatic products in control subjects; and a significant (at least P < 0.05) rise in plasma insulin, C peptide, and glucagon concentrations in relatives of the obese. The high rate of beta-endorphin infusion produced pharmacological elevations of opioid plasma levels in both groups; significant (at least P < 0.05) increments in plasma glucose and glucagon levels and no appreciable modification of plasma insulin and C peptide levels in the control group; and a significant (at least P < 0.05) positive response of plasma glucose, insulin, C peptide, and glucagon levels in relatives of obese subjects. These findings suggest that 1) opioid peptides at least in part play a primary, rather than secondary, role in some metabolic events of obesity; and 2) both physiological and pharmacological plasma levels of beta-endorphin are able to provoke marked islet hormone release in the early phase of human obesity.

Topics: Adult; beta-Endorphin; Blood Glucose; C-Peptide; Female; Glucagon; Humans; Insulin; Kinetics; Male; Obesity; Opioid Peptides

Several studies suggest neuroendocrine abnormalities in, particularly, abdominal, central obesity in humans, a condition with high morbidity and mortality. Therefore the concentrations of neuropeptides and catecholamines in cerebrospinal fluid (CSF) were analysed in 48 obese women, subdivided into groups with central, abdominal and gluteo-femoral distribution of body fat, utilising the waist-to-hip circumference ratio (WHR) for division.. In comparisons with non-obese control women concentration of 5-hydroxyindol acetic acid (5-HIAA), methoxyhydroxyphenylglycol (MHPG), corticotropin releasing hormone (CRH), beta-endorphins (END) and neuropeptide Y (NPY) were lower, while homovanillic acid (HVA) was not different in obese women, HIAA, HVA and END correlated negatively with the WHR only in abdominally obese women, suggesting a threshold effect. HIAA vs HVA as well as CRF vs END correlated strongly in the total and both subgroups. An interrelationship between all these four substances was found in abdominal but not in gluteo-femoral obesity, suggesting a tighter functional coupling in the former group. Several correlations were found between CSF substance levels and appetite registrations, including END vs voracious eating, and for carbohydrate craving vs HIAA and vs HVA (negatively). This was also found only in abdominally obese women.. Although the concentrations of monoamine metabolites and neuropeptides in the CSF sampled at the level of the lumber spine might not be representative for those at regulatory centers in the brain, the findings suggest that low 5-HIAA is characteristic of human obesity, and coupled to CRH as well as eating abnormalities, particularly in abdominal obesity. Since CRH is regulating the balance between the autonomic nervous systems, insulin secretion and thermogenesis in animals, corresponding anomalies in abdominal obesity in humans may have a central origin.

Topics: Adipose Tissue; Adult; beta-Endorphin; Biogenic Monoamines; Body Composition; Body Constitution; Body Mass Index; Corticotropin-Releasing Hormone; Female; Homovanillic Acid; Humans; Hydroxyindoleacetic Acid; Methoxyhydroxyphenylglycol; Middle Aged; Neuropeptide Y; Obesity

Neonatal treatment with monosodium glutamate (MSG) decreases proopiomelanocortin (POMC) peptides and results in obesity. The yellow mouse is a model of obesity induced by the viable yellow (Avy) gene at the agouti locus on Chromosome 2, which results in overproduction of a POMC receptor antagonist. Thus we hypothesized that MSG, when imposed on the genetically susceptible model, would alter the development of obesity. Both yellow obese (Avy) and black lean (alpha/alpha) males were injected on Postnatal Days 1, 3, 5, 7, and 9 with 2.0 mg/g body weight MSG or saline SC. Their food intake, growth parameters, and neurochemical status were examined. Paradoxically, MSG interacted with the yellow phenotype to delay the rapid rate of weight gain characteristic of this model (p < 0.05). Food intake was decreased (p < 0.05) in both phenotypes treated with MSG, as was hypothalamic content of dopamine (p < 0.05) and of the POMC peptide, beta-endorphin (p < 0.001). The yellow obese phenotype was more sensitive than the black lean phenotype to the neurochemical effect of early postnatal MSG administration. Recent reports suggest the agouti locus protein is an antagonist of the receptor for another POMC peptide, melanocyte-stimulating hormone (MSH). Therefore, the balance of functional activity between various POMC peptides appears to be an important factor in the development of both acquired and genetic obesity.

Topics: Animals; Animals, Newborn; beta-Endorphin; Depression, Chemical; Dopamine; Drinking; Eating; Female; Hair Color; Hypothalamus; Mice; Mice, Inbred A; Mice, Inbred C3H; Mice, Inbred C57BL; Obesity; Organ Size; Phenotype; Pro-Opiomelanocortin; Rats; Sodium Glutamate; Weight Gain

Topics: Adult; Atrial Natriuretic Factor; beta-Endorphin; Blood Glucose; Female; Humans; Insulin; Male; Middle Aged; Naloxone; Obesity

Numerous hypothalamic peptides are involved in the control of eating behaviour. We assessed plasma and cerebrospinal fluid (CSF) levels of SRIH, beta-endorphin (beta-EP), CRH, NPY and GHRH in a group of massively obese patients and in normal weight subjects. In the obese patients, CSF SRIH and beta-EP levels were significantly reduced and increased, respectively, compared with controls (20.6 +/- 2.62, mean +/- s.e.m., vs 34.5 +/- 2.14 pg/ml, P < 0.05, for SRIH and 111.2 +/- 5.00 vs 80.4 +/- 5.32 pg/ml, P < 0.001, for beta-EP). Considering the data of obese and control subjects altogether, SRIH and beta-EP concentrations correlated negatively and positively, respectively, with BMI values (r = -0.641, P < 0.005 and r = 0.518, P < 0.05). No significant differences were observed in CSF levels of CRH, NPY and GHRH between obese and normal weight subjects, though GHRH levels were close to the assay sensitivity. CSF concentrations of CRH were positively correlated with those of SRIH in obese patients (r = 0.60, P < 0.05) and with those of NPY both in obese (r = 0.69, P < 0.02) and in control subjects (r = 0.83, P < 0.005). Plasma levels of SRIH, beta-EP, NPY and GHRH did not differ significantly in the two groups of subjects; plasma CRH was undetectable. Our results argue against the hypothesis of an enhanced SRIH tone as the cause of impaired GH secretion in obese patients, a primary defect in GHRH or GH release seems more likely. Moreover, they emphasise the importance of an increased tone of endogenous opioids in the pathophysiology of human obesity.

Topics: Adult; Aged; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Gonadotropin-Releasing Hormone; Humans; Middle Aged; Neuropeptide Y; Obesity; Reference Values; Somatostatin

Autoradiography was used to study the opioid receptors in soleus and extensor digitorum longus (EDL) muscles from normal mice and mice with type II diabetes. Binding sites for [125I]beta-endorphin were present on the surface membranes in muscles from normal mice. The density of receptors was higher in muscles from obese diabetic mice. The specific delta-opioid ligands DPDPE and [D-Ala2]deltorphin-II inhibited the binding of [125I]beta-endorphin whereas mu and kappa agonists did not. Therefore, the opioid receptor present in skeletal muscle fibers of the mouse is of the delta subtype and the number of these receptors is increased in type II diabetes in the mouse.

Topics: Analgesics; Animals; Autoradiography; beta-Endorphin; Binding, Competitive; Cell Membrane; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enkephalin, D-Penicillamine (2,5)-; Enkephalins; Iodine Radioisotopes; Mice; Mice, Obese; Muscle, Skeletal; Obesity; Oligopeptides; Receptors, Opioid, delta; Reference Values

Studies in our laboratory and elsewhere have demonstrated numerous abnormalities of steroid and polypeptide hormone secretion in obesity: hyperestrogenemia and hypogonadotropic hypogonadism in obese men; diminished SHBG levels in both sexes; elevated free testosterone and free estradiol in obese women; PCOS-like gonadotropin and sex-hormone abnormalities in obese women; elevated serum insulin in both sexes; blunted stimulability of prolactin, growth hormone, and vasopressin in both sexes; and elevated basal levels and blunted stimulability and suppressibility of beta-endorphin in both sexes. All of these abnormalities have been clearly shown to be partly or completely reversible with weight loss, with the exception of the endorphin abnormalities. In that area, four out of the five studies reported show no reversibility with weight loss. Reversibility of nearly all the hormonal abnormalities of obesity (i.e., all but the hyperendorphinemia) by weight loss suggests that none of them is causative of obesity. Nevertheless, some of the reversible abnormalities may secondarily amplify the morbidity associated with obesity: the hyperinsulinemia may be related to the increased risk of hypertension, hyperlipidemia, coronary disease, and Type II diabetes; the elevated levels of free estradiol in obese women may be related to their increased risk of breast and endometrial cancer. The role of hyperendorphinemia in obesity clearly requires further investigation, since it is the only observed hormonal abnormality that appears to be non-reversible by weight loss, and also since there seems to be increased sensitivity to beta-endorphin in obesity. The possibility that endorphin abnormalities may be causal in obesity cannot be ruled out.

Topics: Adolescent; Adult; beta-Endorphin; Estradiol; Estrone; Female; Gonadotropins; Hormones; Human Growth Hormone; Humans; Insulin; Male; Middle Aged; Obesity; Prolactin; Sex Hormone-Binding Globulin; Testosterone; Vasopressins

The relationship between maternal plasma levels of beta-endorphin (beta-Ep) during labor and various obstetrical factors was investigated in 115 healthy pregnant women. beta-Ep was determined by radioimmunoassay using double-antibody RIA kit (INCSTAR Corporation, Stillwater, M'S.). The results were as follows: (1) The primiparous women showed a significant increase of maternal plasma levels of beta-Ep at delivery compared with the multiparous women. In addition, the group of women whose Bishop's score at the onset of labor was 5 points or less showed a significant increase of maternal plasma levels of beta-Ep at delivery compared with that in the group of women whose Bishop's score was 6 points or more. (2) The increase in maternal plasma levels of beta-Ep during the first and the second stage of labor was significantly higher in obese women (pre-pregnancy BMI > or = 24) than in normal weight women (pre-pregnancy BMI < 24). In normal weight women in pre-pregnancy, the group of women whose weight gain during pregnancy was 11kg or more showed a significantly higher increase of beta-Ep compared with that in the group of women whose weight gain was less than 11 kg. These results suggest that a stressful delivery caused a significant increase of maternal plasma levels of beta-Ep during labor. Moreover, obesity and marked weight gain during pregnancy caused a remarkable increase in beta-Ep probably due to latent dystocia.

Topics: beta-Endorphin; Female; Humans; Labor, Obstetric; Obesity; Parity; Pregnancy; Pregnancy Complications; Radioimmunoassay; Weight Gain

A large percentage of the normal population does not adhere to a regular exercise program. Little is known about the factors that predict exercise initiation or adherence. This study provides data on the role of psychological, physical, and biological factors in exercise adherence among women.. Twenty-three women participated in a free aerobics program in which they could attend as many exercise sessions as they chose. Psychological and physical measures as well as serum beta-endorphin levels pre- and post-exercise were taken and used to predict total number of exercise sessions attended.. Endorphin levels did not change as a function of exercise and did not predict the number of sessions attended. Rather, women who were overweight, shorter, had several physical complaints, and felt somewhat anxious were most likely to attend the exercise sessions, and these variables accounted for 73% of the variance in sessions attended.. Because psychological and physical discomfort predicted exercise adherence, these results suggest that emphasizing the immediate symptom-relief benefits of exercise might increase initiation and adherence in the general population.

Topics: Affect; Anxiety; beta-Endorphin; Body Height; Exercise; Female; Humans; Multivariate Analysis; Obesity; Patient Compliance; Pilot Projects; Predictive Value of Tests; Sampling Studies

We examined the effects of an oral glucose load on plasma insulin, androgens, and beta-endorphin (beta EP) concentrations in patients carefully selected as having polycystic ovary syndrome (PCOS) and normal glucose tolerance. Our aim was to verify whether insulin resistance is a common feature of PCOS and to differentiate the metabolic abnormalities related to PCOS from those associated with obesity. Plasma immunoreactive insulin (IRI), C-peptide (C-PR), testosterone, androstenedione, dehydroepiandrosterone sulfate, ACTH, and beta EP responses to a 3-h oral glucose tolerance test (OGTT) were evaluated in 10 obese (OB-PCOS) and 10 nonobese (NO-PCOS) patients with PCOS and in 7 obese and 7 nonobese ovulatory controls. OB-PCOS and NO-PCOS did not differ significantly from weight-matched controls in the IRI response, but had a significantly higher C-PR response in terms of mean postglucose load levels and mean incremental areas. During OGTT, mean plasma levels of testosterone, androstenedione, and dehydroepiandrosterone sulfate declined in both PCOS groups as well as in controls, and no significant correlation between the plasma androgen and IRI or C-PR responses was found. The ACTH response in OB-PCOS and NO-PCOS was similar to that in controls, with a progressive decrease until 180 min. A similar decline in plasma beta EP was found in controls, whereas no change in plasma beta EP was observed in OB-PCOS and NO-PCOS. These findings indicate that independently of the presence of obesity, PCOS patients have enhanced insulin secretion in response to OGTT and show a peculiar pattern of changes in plasma beta EP.

Topics: Administration, Oral; Adult; Androgens; Androstenedione; beta-Endorphin; C-Peptide; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Obesity; Polycystic Ovary Syndrome; Radioimmunoassay; Testosterone

The concentrations of beta-endorphin, ACTH, insulin (IRI), glucagon (IRG), cortisol and growth hormone were determined by radioimmunoassay during oral glucose tolerance test (OGTT) performed in 13 obese patients with normal glucose tolerance and without arterial hypertension. The test was performed in random, before and after intravenous administration of 0.8 mg of naloxone. Six persons with normal body weight served as controls. Higher basal concentrations of beta-endorphin and significant increase in beta-endorphin levels during OGTT, without concomitant increase in ACTH concentrations, have been found in obese patients. No effect of naloxone on beta-endorphin liberation during OGTT was observed, though the drug caused lowering in maximal increment of beta-endorphin and paradoxically lowered the concentrations of ACTH and cortisol. The basal concentrations of beta-endorphin did not correlate with the concentrations of insulin, ACTH, cortisol and growth hormone. Elevated concentrations of insulin, lowered concentration of growth hormone and normal levels of glucose and glucagon were observed in basal conditions, and excessive responses of insulin, glucose and glucagon were observed in obese patients during OGTT. Naloxone lowered insulin response and inhibited the fall of growth hormone during OGTT but did not influence the concentrations of glucose and glucagon. No correlation was found during OGTT after naloxone between insulin and beta-endorphin, ACTH or cortisol, whereas negative correlation was observed between insulin and growth hormone. The obtained results suggest that the elevated concentrations of beta-endorphin in simple obesity may be of both hypophyseal and peripheral origin. Hyper-beta-endorphinemia observed in obesity is probably not directly responsible for hyperinsulinemia, it may, however, be responsible for lower sensitivity of tissues to the action of insulin.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Female; Glucose Tolerance Test; Growth Hormone; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Naloxone; Obesity; Radioimmunoassay

The basal and hyperglycaemia-stimulated secretion of glucose, IRI and beta-endorphin (BE) were studied in subjects who had gone surgical treatment for obesity few years ago and the results were compared with those of obese subjects and lean controls. 58 persons were divided into the following groups: A-obese subjects BMI > 30, B--obese subjects 25 < BMI < 30, C--subjects treated by truncal vagotomy and gastric banding, D--subjects treated by jejunoileostomy, E--control group BMI < 25. Oral glucose (75 g) tolerance test was performed in all subjects. Blood concentration of glucose, and serum concentration of IRI and BE were studied before and 30, 60, 90 and 120 minutes after ingestion of glucose. The basal levels and areas over basal values (AOBV) of investigated parameters were evaluated. Both the basal and glucose stimulated levels of IRI and BE were higher in the obese subjects than in the control group. Truncal vagotomy and gastric banding or jejunoileostomy resulted in reduction of IRI secretion without any decrease in BE levels. The alteration of the opioid system may play some role in the pathogenesis of obesity.

Topics: Adult; beta-Endorphin; Female; Glucose Tolerance Test; Humans; Insulin; Jejunoileal Bypass; Male; Middle Aged; Obesity; Reference Values; Vagotomy, Truncal

Obese individuals may be characterized by higher than normal basal and stimulated beta-endorphin plasma concentrations, which suggests an increased activity of the opioid system. This study was carried out to investigate whether the regulation of beta-endorphin secretion may be different in different phenotypes of obesity. Twenty-two obese women (body mass index greater than 30 kg/m2) without other endocrine and metabolic abnormalities were investigated. A group of seven normal weight healthy women matched for age served as controls. According to the protocol, obese women included in the study had a waist-to-hip ratio higher than 0.85 (n = 9) or lower than 0.80 (n = 13). The former were defined as having abdominal type and the latter peripheral type body fat distribution. Both groups were matched for body mass index. All women randomly underwent a corticotrophin-releasing hormone test (human CRF, 1 microgram/kg body weight) and a control saline study, with blood samples for beta-endorphin determination taken at regular intervals. Basal beta-endorphin levels were not significantly different between the three groups. No significant variation in the hormone levels occurred during the control study in either group. After CRF injection, however, beta-endorphin rose significantly in all women, but the hormone concentrations were significantly higher in obese women with abdominal fat distribution than in those with peripheral fat distribution and in controls. These results indicate that, among obese women, only those with the abdominal phenotype seem to have increased opioid activity.

Topics: Abdomen; Adipose Tissue; Adult; Analysis of Variance; Anthropometry; beta-Endorphin; Body Constitution; Body Mass Index; Corticotropin-Releasing Hormone; Female; Follicular Phase; Humans; Obesity; Radioimmunoassay; Time Factors

It has been suggested that a defect in hypothalamic serotonergic neurotransmission may be partly responsible for the impaired pituitary hormone release in obese subjects. In this study we investigated basal serum pituitary hormone concentrations and pituitary hormone release in response to the sequential injection of four hypothalamic releasing hormones before and after a seven-day course of fluoxetine, which inhibits serotonin re-uptake by presynaptic neurons and acts specifically in the brain. Ten obese women (body mass index (BMI) 35.6 +/- 1.0 kg/m2) and nine women of normal weight (BMI 22.9 +/- 0.9 kg/m2) were studied in the early and mid-follicular phases of the menstrual cycle. Basal concentrations of pituitary hormones were measured at 09.00. Subsequently 200 micrograms of TRH and 100 micrograms of CRH, GnRH and GHRH were injected intravenously. The pituitary hormone response was measured at regular intervals until 180 min after the four injections. The experiment was repeated after a seven-day course of 60 mg fluoxetine orally. We found the basal concentrations of prolactin (PRL) and growth hormone to be significantly lower in obese subjects than in the normal controls. Basal concentrations of ACTH, beta-endorphin, TSH, LH and FSH in the two groups were comparable. Releasing hormone-induced responses in the two groups were not significantly different. Administration of fluoxetine "restored" the basal PRL concentrations in obese subjects. It did not affect the other basal hormone concentrations. Furthermore, fluoxetine treatment reduced TRH-induced TSH release in both normal and obese subjects. It did not influence the other releasing hormone-induced responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; beta-Endorphin; Corticotropin-Releasing Hormone; Female; Fluoxetine; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Growth Hormone-Releasing Hormone; Humans; Hypothalamo-Hypophyseal System; Hypothalamus; Luteinizing Hormone; Obesity; Pituitary Gland; Pituitary Hormones; Prolactin; Serotonin; Synaptic Transmission; Thyrotropin

Topics: alpha-MSH; Animals; beta-Endorphin; Diabetes Mellitus; Diabetes Mellitus, Experimental; Gene Expression; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Mice, Obese; Motor Neurons; Muscles; Obesity; Pro-Opiomelanocortin

Topics: Adrenocorticotropic Hormone; Animals; beta-Endorphin; Binding Sites; Diabetes Mellitus; Diabetes Mellitus, Experimental; Male; Mice; Mice, Inbred Strains; Mice, Obese; Muscles; Obesity; Receptors, Corticotropin; Receptors, Opioid; Receptors, Pituitary Hormone; Reference Values

Immunoreactivity for two derivatives of pro-opiomelanocortin, beta-endorphin and alpha-melanocortin (or corticotropin), was demonstrated, using a conventional immunoperoxidase method, in some of the intramuscular nerves in muscle sections from obese diabetic (ob/ob) mice and homozygous lean (+/+) mice. The endplate regions were visualized in the sections by staining for acetylcholinesterase reaction product. The proportion of muscle endplates with beta-endorphin-immunoreactive motor nerves was approximately 2.5-fold higher in soleus and extensor digitorum longus muscles and approximately 1.5-fold higher in the diaphragm of the obese (ob/ob) mice compared to the normal lean mice. The proportion of muscle endplates with alpha-melanotropin-immunoreactive motor nerves was between 30 and 53% lower, depending on the muscle type, in the ob/ob mice compared to the lean mice. The muscles of ob/ob and lean mice were investigated for the presence of specific binding sites for [125I]beta-endorphin and for [125I]corticotropin, using autoradiography. Some muscle fibres in soleus, extensor digitorum longus and diaphragm in both the ob/ob and the lean mice exhibited specific binding sites for the radioactive ligands. The binding sites were distributed over the entire surface in these muscle fibres. In the ob/ob mice the number of muscle fibres with specific [125I]beta-endorphin binding sites was six-fold higher in soleus and approximately 10-fold higher in extensor digitorum longus and diaphragm, than in the corresponding muscles of the lean mice. In contrast, the number of muscle fibres with specific [125I]corticotropin binding sites was similar in obese (ob/ob) and lean mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; alpha-MSH; Animals; Autoradiography; beta-Endorphin; Binding Sites; Diabetes Mellitus; Diabetes Mellitus, Experimental; Immunoenzyme Techniques; Iodine Radioisotopes; Mice; Mice, Inbred C57BL; Mice, Obese; Motor Endplate; Muscles; Obesity; Receptors, Corticotropin; Receptors, Opioid; Receptors, Pituitary Hormone; Reference Values

Topics: Adult; beta-Endorphin; Blood Glucose; Corticotropin-Releasing Hormone; Female; Glucagon; Humans; Insulin; Islets of Langerhans; Middle Aged; Obesity

The present study was undertaken to evaluate the metabolic and hormonal responses to physiologic elevations of plasma beta-endorphin concentrations in both normal-weight and obese healthy subjects. The infusion of synthetic human beta-endorphin (4.5 ng/kg/min) produced the following: (1) in normal-weight subjects, no significant change of plasma glucose and pancreatic hormones (insulin, C-peptide, and glucagon), a significant plasma free fatty acids (FFA) increase, and a suppression of glycerol plasma levels; (2) in obese subjects, significant increases of glucose, insulin, C-peptide, and glucagon, a progressive decline of circulating FFA, and no change in glycerol plasma levels. In obese subjects, the intravenous administration of naloxone, given as a bolus (5 mg injected in 5 minutes) before the start of beta-endorphin infusion, reduced the plasma glucose response to the opioid by approximately half, annulled the pancreatic hormonal responses, and also reduced the FFA, but not glycerol, response. In normal-weight subjects, naloxone pretreatment did not induce any change of the flat glucose and hormonal responses to beta-endorphin, but reversed its effects on circulating FFA and glycerol. These data suggest that physiological elevations of plasma beta-endorphin concentrations produce metabolic and hormonal effects in obese subjects significantly different from those occurring in normal-weight subjects; these effects are partially naloxone-sensitive, suggesting the mediation of endogenous opioid receptors.

Topics: Adult; beta-Endorphin; Blood Glucose; Body Weight; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Kinetics; Male; Obesity; Reference Values

It has been demonstrated that opioid peptides are involved in the stimulation of food intake in rats and that the circulating beta-endorphin levels are increased in genetically obese rodents. Therefore, to assess whether the changes in food intake may influence circulating beta-endorphin levels in obese subjects, plasma beta-endorphin, ACTH and cortisol concentrations were determined in obese patients after an oral glucose load and during a 7-day total starvation. Baseline plasma beta-endorphin concentrations were significantly higher in obese patients than in control normal-weight subjects, while ACTH and cortisol levels were similar in both groups. Plasma beta-endorphin, ACTH and cortisol concentrations were not affected by the ingestion of 75 g glucose, neither were plasma beta-endorphin concentrations modified during prolonged starvation. Moreover, the lack of nycthemeral variations in beta-endorphin levels, documented before and during starvation while plasma ACTH and cortisol were significantly reduced in the evening, suggests that some extra anterior pituitary sources or some obesity-related changes in beta-endorphin metabolism may contribute to the pool of circulating beta-endorphin in obese subjects. On the other hand, even the extreme changes in nutritional conditions, such as total food deprivation or glucose ingestion, are devoid of any detectable influence on circulating beta-endorphin levels.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Circadian Rhythm; Eating; Fasting; Female; Glucose; Glucose Tolerance Test; Humans; Hydrocortisone; Male; Obesity

To test the hypothesis that the hyperendorphinaemia in obesity originates from outside the pituitary.. Intravenous administration of corticotrophin-releasing hormone (CRH) after overnight suppression with 2 mg of dexamethasone in normal-weight controls and in obese subjects before and after weight reduction.. Eleven obese females, age (mean +/- SEM) 30 +/- 2.1 years, body mass index (BMI) 41.2 +/- 1.9 kg/m2. Eight normal-weight females served as controls, age 26 +/- 2.1 years, BMI 21.4 +/- 0.5 kg/m2. Five obese subjects were also studied after weight loss of 18.4 +/- 1.0% of original weight.. Plasma beta-endorphin, ACTH and cortisol. Cortisol production rate in 24-hour urine. Basal (without dexamethasone suppression) plasma beta-endorphin levels.. Basal (without dexamethasone suppression) beta-endorphin levels were 7.7 +/- 0.8 pmol/l in the obese and 3.8 +/- 0.5 pmol/l in the control subjects (P less than 0.005). The degree of suppression of beta-endorphin after dexamethasone was similar in the obese (23.2 +/- 3.7%) and in the control subjects (28.2 +/- 0.12%). Administration of CRH following dexamethasone suppression resulted in a small but significant increase of plasma beta-endorphin in both obese (from 1.55 +/- 0.12 to 2.32 +/- 0.28 pmol/l) and control subjects (from 0.98 +/- 0.24 to 1.69 +/- 0.33 pmol/l). The groups did not differ regarding this response, nor regarding the release of ACTH and cortisol after CRH. Cortisol production rate was higher (P less than 0.001) in the obese (68.7 +/- 3.3 mumol/24 h) than in the controls (40.0 +/- 3.0 mumol/24 h). No correlation between cortisol production rate and basal beta-endorphin levels was found. Weight loss appeared to have no influence on cortisol production rate, basal beta-endorphin levels, or on the responses to dexamethasone or CRH.. Plasma beta-endorphin in obese subjects can be affected by manipulations of the hypothalamic-pituitary-adrenocortical axis; the hypothesis that the hyperendorphinaemia of obesity originates from outside the pituitary cannot be confirmed.

Topics: Adult; beta-Endorphin; Corticotropin-Releasing Hormone; Dexamethasone; Female; Humans; Hypothalamo-Hypophyseal System; Obesity; Pituitary-Adrenal System; Weight Loss

The responses of plasma beta-endorphin, insulin and glucose to two different isocaloric mixed meals--high carbohydrate (CHO meal) and high fat (fat meal)--were assessed in women with android obesity before (n = 11) as well as after (n = 5) weight reduction, and in normal-weight controls (n = 8). Basal plasma beta-endorphin concentrations in the obese subjects (7.7 +/- 1.2 pmol/l) were significantly (p less than 0.005) higher than in the controls (3.8 +/- 0.5 pmol/l) and were not influenced by weight loss. Fasting plasma levels and the integrated releases of insulin and glucose, both after the CHO meal and after the fat meal were significantly higher in the obese subjects than in the controls. The fat meal induced no changes in beta-endorphin levels in either group. After the CHO meal a significant decrease in plasma beta-endorphin concentration was observed only in the obese group before weight reduction. An influence on beta-endorphin release by macronutrients is hypothesized.

Topics: Adult; beta-Endorphin; Blood Glucose; Dietary Carbohydrates; Dietary Fats; Energy Intake; Fasting; Female; Food; Humans; Insulin; Kinetics; Obesity

Beta-endorphin (beta-Ep) plasma levels are higher in obese patients than in normal subjects. To establish that this finding constitutes hyperendorphinemia, 28 obese patients aged 12-55 years, six males and 22 females, (weighing 61-117 kg) were investigated twice by an overnight 1-mg p.o. dose dexamethasone suppression test (DST) before and after weight loss. beta-Ep was measured by radioimmunoassay (RIA). Before body weight loss, beta-Ep was higher than normal and unresponsive to DST, whereas ACTH and cortisol were suppressible. After weight loss, beta-Ep was slightly reduced but still insensitive to DST. ACTH and cortisol were responsive as usual. Findings suggest a resistance to DST in obesity as far as beta-Ep is concerned. The disorder persists even after weight loss, indicating that hyperendorphinemia is not secondary to body weight excess. Accordingly, one can argue that the unresponsiveness of the endorphinergic system to its physiological feedback is a pathophysiological characteristic of obesity.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Body Weight; Dexamethasone; Feedback; Female; Humans; Hydrocortisone; Male; Middle Aged; Obesity; Radioimmunoassay; Weight Loss

It is speculated that endogenous opioid peptides are involved in glucose metabolism and that their homeostasis might be disturbed in obesity. Despite a different response of the pancreatic beta-cells after beta-endorphin and naloxone injections between obese patients and normal weight controls, there is little knowledge concerning the direct influence of a glucose load on beta-endorphin plasma levels, especially with respect to various nutrition states. During exploration of this topic we gained further insight on the difference of basal beta-endorphin plasma levels between normal and overweight persons. We compared beta-endorphin plasma levels during an oral glucose load in 60 obese, non-diabetic patients and in 20 normal weight controls. We also studied 40 of the obese patients after a weight reduction of 2.1 kg/m2. The following results were obtained: (1) Normal weight females have significantly lower (P less than 0.05) basal beta-endorphin levels compared to the male controls. This difference in gender is abolished in obesity where female and male patients do not differ in basal beta-endorphin plasma levels. Therefore, the difference between normal and overweight persons in beta-endorphin plasma levels was restricted to the subgroup of females. We suppose that former neglect of this difference in gender explains most of the so far reported discrepant results. (2) During the oral glucose tolerance test the beta-endorphin plasma values remained constant in the obese group. Despite improved insulin sensitivity after weight reduction there was still no change of beta-endorphin plasma levels both during the OGTT and when compared to the values before weight reduction.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; beta-Endorphin; Blood Glucose; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Middle Aged; Obesity; Sex Characteristics; Weight Loss

The responses of plasma glucose, insulin, C-peptide and glucagon to an infusion of human beta-endorphin (0.5 mg/h) were studied in 10 formerly obese subjects who had lost 35 kg by dieting (body mass index less than 25) and compared with those of 10 normal-weight control (body mass index less than 25) and 10 obese (body mass index greater than 30) subjects. The fasting plasma concentrations of beta-endorphin were significantly higher in both the obese and the post-obese group than in the control group. In both obese and post-obese subjects, the infusion of beta-endorphin caused significant increases in peripheral plasma glucose, insulin, C-peptide and glucagon concentrations. In the control group, matched for age, sex and weight with the formerly obese group, there was no appreciable change in plasma insulin and C-peptide concentrations during the infusion of beta-endorphin, but the rise in plasma glucose was more sustained. Thus, 1. the increased plasma beta-endorphin concentrations found in human obesity are not corrected by normalization of body weight; and 2. formerly obese, normal-weight subjects behave as obese subjects in their metabolic and hormonal responses to beta-endorphin infusion. The alteration of the opioid system in human obesity may play some role in the predisposition to weight gain.

Topics: Adult; beta-Endorphin; Blood Glucose; Body Weight; C-Peptide; Female; Glucagon; Humans; Insulin; Kinetics; Male; Obesity

Forty obese subjects with normal glucose tolerance test (NGTT) thirteen diabetic obese subjects and sixteen normal subjects were studied to evaluate the possible interactions between beta-endorphin (B-Ep) and glucose homeostasis. On the basis of baseline B-Ep levels, two subgroups were selected: one group with normal mean values of B-Ep (7.02 +/- 0.59 pmol/l); another group with elevated mean values of B-Ep (18.95 +/- 1.52 pmol/l). No differences between these subgroups were found as regards body mass index (BMI), insulin and glucagon levels. Normal B-Ep values were found in diabetic obese subjects. No significant correlation was found between B-Ep and BMI, insulin or glucagon. Considering that B-Ep is involved in eating behavior and on the basis of our results, we suggest that elevated B-Ep levels can be found only in those obese NGTT subjects whose obesity is probably related to an abnormal modulation of food intake, such as hyperphagia.

Topics: Adult; beta-Endorphin; Blood Glucose; Diabetes Mellitus; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Male; Obesity

The nature of the primary genetic defects in ob/ob and db/db mice are unknown. Both the obese (ob) and diabetes (db) mutations produce similar, multicomponent obese-hyperinsulinemic syndromes when maintained in the same strain of mouse. In an attempt to find differences between these mutations in neuroendocrine function affecting the islets of Langerhans or the pituitary, tissue content of four neuropeptides that are known to be capable of influencing the rate of insulin secretion was examined in obese (ob/ob) and diabetes (db/db) mice. In the first study, C57BL/6Job/ob and control males were studied at 3, 4, and 11 weeks of age. In the second study, db/db mice of both sexes and two inbred strains (C57BL/6J and C57BL/KsJ), which differ markedly in the severity of expression of the diabetes phenotype, were studied at 3 weeks of age, before the development of hyperglycemia and secondary consequences thereof. Immunoreactive peptides were measured in acetic acid extracts of pancreas and pituitary. No differences between male ob/ob and db/db mice of the C57BL/6J strain were found. Marked sex differences in lean control mice were found at 3 weeks of age in pancreatic Met-enkephalin-LI and galanin-LI (with two- to threefold higher content in males). Low pancreatic content (50% to 70% lower than in control mice) of galanin-LI, Met-enkephalin-LI and Leu-enkephalin-LI was associated with hyperinsulinemia in male B6 ob/ob and db/db mice at 3 weeks of age, though not in B6 db/db females and not in BKs db/db mice of either sex.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; beta-Endorphin; Diabetes Mellitus, Experimental; Enkephalin, Leucine; Enkephalin, Methionine; Female; Galanin; In Vitro Techniques; Insulin; Male; Mice; Mice, Mutant Strains; Mice, Obese; Neuropeptides; Obesity; Pancreas; Peptides; Pituitary Gland; Reference Values; Sex Factors; Species Specificity

In seventy-two patients affected by hyperphagic obesity and forty age-matched, normal weight volunteers we performed a psychological assessment, through various mental tests, and evaluated the beta-endorphin (B-Ep), ACTH and cortisol circulating levels, in basal condition and following an overnight short dexamethasone suppression test (DST). The hormones were measured by radioimmunoassay either directly in the serum (cortisol) and the plasma (ACTH), or after affinity gel column chromatography (B-Ep). In obese subjects B-Ep levels in basal conditions were four times greater than in normal weight controls and showed significantly less reduction after DST. ACTH and cortisol levels, in contrast, were in the normal range and were suppressed following dexamethasone as was also true in the control group. Psychological evaluation on M.M.P.I. (Minnesota Multiphasic Personality Inventory) revealed a trend toward hypochondria, depression, hysterias, psychoasthenia and schizophrenia. However, no significant correlation has been found between M.M.P.I. clinical scale scores and circulating levels of B-Ep and cortisol either in basal conditions or after DST. In conclusion, these data do not support the hypothesis that abnormalities of the hypothalamus-pituitary-adrenal axis in hyperphagic obesity are related to affective disorders.

Topics: Adrenocorticotropic Hormone; Adult; Affective Symptoms; Anxiety; beta-Endorphin; Depression; Dexamethasone; Endorphins; Female; Humans; Hydrocortisone; Hyperphagia; Male; Middle Aged; Obesity; Personality Tests

Circulating levels of cortisol and beta-endorphin were evaluated in basal condition and following dexamethasone administration in 20 healthy subjects and in 60 subjects suffering from hyperphagic obesity. Moreover, mental tests were administered to these subjects in order to evaluate the affective state. Our data showed that in obese patients B-Ep plasma levels were significantly higher than those of the control group, while cortisol plasma levels were similar in the two groups. Dexamethasone administration decreased cortisol plasma levels in normal and obese subjects, while did not modify B-Ep plasma levels in obese subjects. However, after dexamethasone administration 16.6% of the obese subjects did not show a complete decrease of cortisol level. This group of subjects obtained the highest scores for depression and hypochondria to MMPI.

Topics: Adult; beta-Endorphin; Depressive Disorder; Dexamethasone; Female; Humans; Hydrocortisone; Hyperphagia; Male; Obesity

In order to clarify a possible relationship between opioid peptides and glucose homeostasis in obesity we studied Beta-Endorphin (B-Ep), ACTH, cortisol and insulin plasma levels in response to an oral glucose tolerance test (OGTT) in 8 subjects after a hypocaloric diet for 90 days. We obtained through this treatment a weight loss superior to 30% of the initial weight excess (WE) compared with ideal body weight. Moreover, we compared the obtained results with our preliminary study that was performed with the same protocol but without caloric restriction. B-Ep was measured by RIA after silicic acid extraction and G75 Sephadex column chromatography. ACTH, insulin and cortisol were measured directly on plasma by an RIA method. Basal and during OGTT-induced levels of glucose, insulin, ACTH and cortisol decreased in comparison with the values obtained before diet. Conversely, B-Ep remained higher than normal both in the basal condition and during OGTT, and showed values consistently similar to those before diet. These data show that hyperinsulinemia is corrected by weight loss, while hyperbetaendorphinemia remains unchanged. Accordingly, it can be suggested that no direct relationship occurs between hyper-B-Ep-hyper-IRI in obesity. A further insight into the role of hyper-B-Ep in obesity is, thus, necessary, assuming as hypothesis that the increase in B-Ep may be a cause and not a corollary of the polymorphic aspects of obesity.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Blood Glucose; Female; Glucose Tolerance Test; Homeostasis; Humans; Hydrocortisone; Insulin; Middle Aged; Obesity; Radioimmunoassay; Weight Loss

It is now well-known that the plasmatic levels of beta-endorphin (B-Ep) in subjects suffering from hyperphagie obesity during childhood, adolescence and adult age, are higher than those of normal weight standard-wright. The causes are still unknown. In obese subjects, there is also a dissociation between plasmatic levels of B-Ep and of ACTH, in spite of the common origin of Proopiomelanocortin (POMC). On the basis of these observations we studied the plasmatic levels of B-Ep, ACTH and cortisol, basal and after DXM, before and after the reduction of body weight. With the aim of evaluating pharmacological interference, the obese subjects were treated with diet alone or diet associated with an anorectic and serotoninergic drug (fenfluramin). The results have shown that after slimming, obtained with diet alone or with the help of the serotoninergic drug, the hyperendorphinemia persists both in basal conditions and after the DXM test. The verification of such behaviour in some psychiatric diseases supports our assumption of a link between hyperendorphinemia, behaviour alterations, hyperphagy and obesity.

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Female; Humans; Hydrocortisone; Male; Obesity

Topics: Adult; beta-Endorphin; Body Mass Index; Female; Glucagon; Glucose Clamp Technique; Humans; Hyperglycemia; Insulin; Male; Middle Aged; Obesity

Several reports have shown elevated circulating beta-endorphin (beta-EP) levels in patients with polycystic ovarian disease (PCOD). However, it is not yet clear whether these high beta-EP levels are linked to the etiopathogenesis of PCOD or are secondary to the obesity. In the present study we measured beta-EP plasma concentrations in 19 PCOD patients, 10 with normal weight (Group A) and 9 with excessive weight (Group B), and in 18 normally ovulating women, 10 with normal weight (Group C) and 9 with excessive weight (Group D). beta-EP values were similar in the two groups of non-obese patients and controls. beta-EP concentrations were also similar in the two groups of obese patients and controls, and they were significantly higher (p less than 0.05) than in non-obese patients. Our data indicate that in PCOD, elevated beta-EP values are related to obesity, suggesting that they are not linked to the pathogenesis of PCOD.

Topics: Adolescent; Adult; beta-Endorphin; Female; Follicle Stimulating Hormone; Humans; Luteinizing Hormone; Obesity; Polycystic Ovary Syndrome; Sex Hormone-Binding Globulin

The equilibrium dissociation constants and maximal binding capacities of 3H-dihydromorphine (DHM), 3H-D-Ala2-D-leu3-enkephalin (DADL), and 3H-dynorphin A(1-8) for their respective mu, delta, and kappa opiate binding sites were studied in brain membrane preparations from lean and genetically obese-hyperglycaemic (Aston ob/ob) mice. The concentration of kappa binding sites was 2.7 fold higher in obese compared with lean mouse brain (231 +/- 44.6 versus 83.8 +/- 10.3 fmoles 3H-dynorphin/mg protein respectively, mean +/- SEM). The concentration of delta binding sites in obese was 1.6 fold that in lean mouse brain (94.5 +/- 8.6 versus 59.5 +/- 6.5 fmoles 3H-DADL/mg protein). In contrast, the concentration of brain mu receptors was 40% lower in obese compared with lean mice (20.8 +/- 2.19 and 34.8 +/- 3.1 fmoles 3H-DHM/mg protein respectively). Binding affinities of delta and kappa sites for their respective ligands were not significantly different in lean v. obese mice. However, for mu sites, lean mouse binding data showed two affinities, one was not significantly different from obese (0.35 nM) the second was lower (1.18 nM) for DHM. Increases of approximately 5 fold and 3 fold in the brain content of beta-endorphin and met-enkephalin respectively, and no differences in brain dynorphin levels, were demonstrated in obese mice compared with lean controls. In obese mice, pituitary beta-endorphin content was 9 fold higher, met-enkephalin 4 fold higher and dynorphin 12 fold higher than in lean mice. The striking differences in opioid binding-site characteristics and in endogenous opioid peptide levels in obese compared with lean mice may contribute to the hyperphagia and, directly or indirectly, to the development of hyperglycaemia and hyperinsulinaemia in obese mice.

Topics: Animals; beta-Endorphin; Binding Sites; Brain; Brain Chemistry; Endorphins; Enkephalin, Methionine; Mice; Obesity; Pituitary Gland; Reference Values; Tissue Extracts

Previous reports have provided suggestive evidence for a role of endogenous opiates in modulating feeding behavior as well as insulin secretion from the pancreas. This evidence includes pharmacologic studies as well as studies of endogenous opioid peptides in tissues of genetically obese rodent models. In the present study, content of three opioid peptide immunoreactivities (beta-endorphin, met-enkephalin and leu-enkephalin) were measured in pituitary and pancreas of two recently described, genetically obese rats, the LA/N-cp and the SHR/N-cp. Although both of these inbred strains carry the same cp allele, the SHR-cp rat is obese and diabetic by 8 weeks of age, while the LA/N-cp is obese but remains euglycemic. There were no significant differences in content of immunoreactive beta-endorphin, met-enkephalin or leu-enkephalin in whole pituitary, posterior or anterior lobes of the pituitary, or pancreas which could be ascribed to the effect of the obese phenotype. These data are in contrast to previously reported studies in which significant alterations in opioid peptide immunoreactivities were found in genetically obese Zucker fa/fa rats, C57BL/6 ob/ob mice and C57BL/Ks db/db mice. The present work provides no support for pathological involvement of opioid peptides in the genetically obese cp/cp rat.

Topics: Animals; beta-Endorphin; Enkephalin, Leucine; Enkephalin, Methionine; Male; Obesity; Pancreas; Pituitary Gland; Rats; Rats, Inbred SHR

The relationship between beta-endorphin(beta-EP)/beta-lipotropin(beta-LP) and insulin secretion in the basal state and after glucose challenge was studied in obese male Zucker rats and their lean littermates. Baseline plasma beta-EP/beta-LP concentrations were similar in the two groups of animals. Baseline plasma insulin and serum glucose concentrations were significantly higher in the obese animals. Following glucose challenge, the increase in plasma beta-EP/beta-LP concentrations was significantly lower in the obese animals than in their lean littermates. Opioid blockade with naloxone failed to alter the baseline hyperinsulinemia and hyperglycemia seen in the obese animals. The data suggest that the hyperinsulinemia in the obese Zucker rat is not due to endogenous hyperendorphinemia as shown in humans with polycystic ovary syndrome. The obese rats showed dissociation between glucose-stimulated plasma levels of beta-EP/beta-LP and insulin levels which may contribute to the hyperinsulinemia and insulin resistance in these animals.

Topics: Animals; beta-Endorphin; beta-Lipotropin; Blood Glucose; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Secretion; Male; Obesity; Radioimmunoassay; Rats; Rats, Mutant Strains; Rats, Zucker

In order to evaluate the role of beta-endorphin in the pathogenesis of obesity and essential hypertension 44 subjects were investigated: 12 nonobese hypertensives, 11 obese hypertensives, 11 obese normotensives and 10 normal subjects. Plasma concentrations of beta-endorphin and cortisol were measured by radioimmunological and ACTH by immunoradiometric methods. The plasma concentrations and the circadian rhythms of ACTH and cortisol secretion were normal in all groups investigated. A circadian rhythm of beta-endorphin secretion was demonstrated in nonobese hypertensives and in normal subjects. The plasma concentrations of beta-endorphin were twice higher than those in nonobese subjects. Also, in all obese patients the circadian rhythm of beta-endorphin secretion was blunted. The increased concentrations and the altered circadian rhythm of beta-endorphin in all obese subjects may point to a role of beta-endorphin in the pathogenesis of obesity rather than in that of essential hypertension.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Circadian Rhythm; Humans; Hydrocortisone; Hypertension; Obesity

Patients with simple exogenous obesity are characterized by increased B-endorphin (B-EP) plasma levels, despite normal ACTH and B-Lipotropin (B-LPH). To evaluate the origin of such an hyperendorphinemia, 42 obese patients were submitted to a short overnight dexamethasone suppression test (DST: 1 mg at 23:00 h). Blood samples were taken in basal conditions and 9, and 17 h after DST. The same procedure was applied in 12 healthy, normal weight volunteers. In further five patients, 0.5 mg per 4/die were given. B-EP was measured by radioimmunoassay (RIA) after silicic acid extraction and Sephadex G-75 column chromatography. ACTH and Cortisol were measured by direct IRMA and RIA, respectively. Basal B-EP levels of patients (24.2 +/- 16.5, fmol/ml, M +/- SD) were double than in normal weight controls (10.8 +/- 4.6), while ACTH and cortisol fell in the normal range. ACTH and cortisol were significantly reduced by DST in both patients and controls, while B-EP in patients did not. Cortisol, however, was not suppressed in 7 patients (16%). At 08:00, the suppression of B-EP in controls was 49.0 +/- 18.4%, while in obese patients it was only 21.2 +/- 38.8% (p less than 0.01). However, patients with weight excess below 50% normally suppressed B-EP (41.6 +/- 15.3%), while those with weight excess over 75% did not (11.3 +/- 47.5%). The doubling of dexamethasone intake does not lead to a suppression of plasma B-EP in these last patients. These data indicate the existence of neuroendocrine abnormalities in the hypothalamus-pituitary-adrenal axis of obese patients and suggest that their hyperendorphinemia originates outside the anterior pituitary.

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Child; Dexamethasone; Female; Humans; Hydrocortisone; Male; Middle Aged; Obesity; Pituitary-Adrenal Function Tests

B-Endorphin (B-Ep), ACTH and cortisol circulating levels, before and after a two months therapy with a hypocaloric diet and an increase in physical exercise, were measured by RIA in 17 obese female subjects. After therapy, the body weight excess fell from 56.6 +/- 22.2% to 38.6 +/- 22.1% (p less than 0.01). Plasma levels of B-Ep decreased from 18.3 +/- 12.5 fmol/ml to 6.4 +/- 3.5 fmol/ml (p less than 0.01); those of ACTH from 46.8 +/- 22.8 pg/ml to 31.2 +/- 11.6 pg/ml (p less than 0.01); and those of cortisol from 15.9 +/- 4.6 micrograms% to 10.3 +/- 2.5 micrograms% (p less than 0.01). The reduction of the elevated plasma B-Ep levels found in obese subjects is related principally to the diet therapy. Thus, as shown in experimental animals, excessive feeding results in an increased hypothalamic-pituitary secretion of B-Ep.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Body Weight; Diet, Reducing; Energy Intake; Female; Humans; Hydrocortisone; Obesity; Physical Exertion

In order to evaluate the secretion of beta-endorphin in obese children and adolescents, we measured plasma beta-endorphin, ACTH and cortisol levels before and following administration of CRH (1 microgram/kg). Fourteen normal weight and 22 obese subjects (weight excess ranging from 30 to 98%) were studied. Plasma hormone levels were measured by radioimmunoassay directly in plasma (cortisol, ACTH) and after silicic acid extraction and Sephadex G-75 column chromatography (beta-endorphin). Basal beta-endorphin levels in obese children were significantly higher than in controls (14.7 +/- 1.8 vs 6.0 +/- 0.6 pmol/l; mean +/- SEM). No differences were found in basal ACTH and cortisol levels. CRH administration significantly increased beta-endorphin, ACTH and cortisol levels in normal subjects and ACTH and cortisol levels in obese subjects. Plasma beta-endorphin levels in obese children and adolescents did not show any significant increment. These data confirm the higher than normal beta-endorphin plasma levels in obese subjects in childhood and demonstrate that CRH is unable to increase beta-endorphin levels, suggesting an impairment of the hypothalamo-pituitary control mechanisms or an extra-anterior pituitary source.

Topics: Adolescent; Adrenocorticotropic Hormone; beta-Endorphin; Child; Corticotropin-Releasing Hormone; Humans; Hydrocortisone; Obesity

Populations eating low-fat or low-fat, high-fiber diets have lower mortality rates for many cancers and coronary heart disease. The importance of nutrient composition in the lumen on absorption and on function of the gastrointestinal tract as a factor in the development of these diseases has not been studied. We investigated the plasma levels of gut-CNS peptide hormones in lean and obese Dutch women fed a high-fat meal and administered cholecystokinin (CCK). After a high-fat meal the increase in plasma CCK was similar in lean and obese women. CCK administration significantly decreased insulin release in lean and obese women, decreased glucagon release in obese women, but caused a rapid increase in plasma glucagon in lean women. Although the CCK response was similar to a fat meal in lean and obese women, differences in the control of peptide hormone release occurred in response to fat meals and CCK administration.

Topics: beta-Endorphin; Cholecystokinin; Cholesterol; Coronary Disease; Diet; Diet, Vegetarian; Dietary Fiber; Female; Gastrins; Glucagon; Humans; Insulin; Lipids; Middle Aged; Neoplasms; Obesity; Risk Factors

Catecholamines and endogenous opioid peptides are released in response to stress. Exogenous infusions of epinephrine and beta-endorphin (both in doses of 15, 50, and 80 ng/kg.min sequentially, each dose lasting 30 min) were used to mimic short term stress in both normal weight (body mass index, less than 25 kg/m2) and obese (body mass index, greater than 30 kg/m2) subjects. Fasting plasma insulin, C-peptide, and beta-endorphin concentrations were significantly higher in the obese than in the normal subjects (P less than 0.01-0.005). In lean subjects epinephrine produced significant increases in plasma glucose levels, but no appreciable changes in plasma insulin, C-peptide, or glucagon. Infusion of beta-endorphin in the same subjects caused plasma glucose and glucagon to rise, but insulin and C-peptide levels did not change. The simultaneous infusion of epinephrine and beta-endorphin produced a glycemic response which, although greater, was not significantly different than the sum of the responses to the individual hormone infusions. However, the two hormones had a synergistic interaction on plasma glucagon levels [total glucagon response, 2275 +/- 370 pg/min.mL (ng/min.L); sum of single effects, 750 +/- 152 (+/- SE) pg/min.mL (ng/min.L); P less than 0.01]. The plasma epinephrine [207 +/- 21, 607 +/- 70, and 1205 +/- 134 pg/mL (1130 +/- 115, 3640 +/- 382, and 6577 +/- 691 pmol/L] and beta-endorphin [875 +/- 88, 1250 +/- 137, and 1562 +/- 165 pg/mL (250 +/- 25, 358 +/- 39, and 447 +/- 47 pmol/L] concentrations attained during the infusions of each single hormone were not different from those recorded during the combined hormonal infusion. In obese subjects epinephrine raised plasma glucose levels and caused dose-related increments of plasma glucagon concentrations. Plasma insulin and C-peptide concentrations remained low and rebounded at the end of the infusions. In the same subjects, beta-endorphin produced elevations of plasma glucose, insulin, C-peptide, and glucagon. When the combined hormonal infusion was given to obese subjects, the plasma epinephrine and beta-endorphin concentrations rose to values not significantly different from those in normal weight subjects. However, there was a dramatic increase in plasma glucose exceeding 200 mg/dL (11.1 mmol/L), which remained elevated 30 min after the infusion. The glucagon response was not greater than the sum of the single effects.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Adult; beta-Endorphin; Blood Glucose; C-Peptide; Epinephrine; Female; Glucagon; Humans; Infusions, Intravenous; Insulin; Male; Obesity

Plasma B-Endorphin (B-EP), Growth Hormone (GH) and cortisol response to 100 mcg/m2 b.s., i.v. clonidine (an alpha 2-adrenergic agonist) were evaluated in 17 normal weight children (8 prepubertal and 9 pubertal) and in 15 children with simple exogenous obesity (7 prepubertal and 8 pubertal, weight excess ranging from 29% to 97%). All the hormones were measured by radioimmunoassay either directly in the plasma (GH and cortisol) or after extraction and chromatography (B-EP). Obese prepubertal and pubertal children showed basal B-EP levels significantly higher than in controls and no differences were found in GH and cortisol levels. While in controls clonidine stimulated a significant release of plasma GH and B-EP in obese patients, irrespective of pubertal development, no changes were found. Cortisol levels decreased in both groups. These data suggest an impaired adrenergic control of GH and B-EP secretion in children with simple exogenous obesity.

Topics: beta-Endorphin; Child; Clonidine; Female; Growth Hormone; Humans; Hydrocortisone; Male; Obesity

Topics: Adult; beta-Endorphin; Female; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Insulin; Obesity; Prolactin

Topics: Animals; beta-Endorphin; Body Weight; gamma-Aminobutyric Acid; Insulin; Obesity; Rats; Rats, Zucker; Valproic Acid

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Female; Humans; Male; Middle Aged; Obesity

Topics: Animals; beta-Endorphin; Brain; Cholecystokinin; Endorphins; Hypothalamus; Mice; Neuropeptides; Neurotransmitter Agents; Obesity

In order to evaluate the role of opiate, dopaminergic and adrenergic systems in the mechanism of hypothalamo-pituitary disturbances in obesity, 9 obese women and 14 healthy women were investigated. Serum GH, LH, beta-endorphin and cortisol concentrations were measured after administration of clonidine, an alpha 2-adrenergic receptor agonist, and naloxone, an opiate antagonist. Additionally, PRL levels were measured after administration of the dopamine receptor blocker metoclopramide. An impaired GH response to clonidine and naloxone was found in obese women. However, a marked increase in beta-endorphin was observed in obese patients after clonidine administration. Naloxone did not cause any significant change in beta-endorphin release. Neither clonidine nor naloxone induced any change in LH release. Serum PRL concentrations in response to metoclopramide were significantly higher in obese patients than in healthy women.. Disturbed activity in opiate, adrenergic, and dopaminergic systems may be of pathogenetic importance in a hypothalamo-pituitary dysfunction in obesity. The occurrence of hypothalamic amenorrhoea as well as the presence of abnormalities of the central nervous system regulation of GH, PRL, ACTH, cortisol, insulin and vasopressin output might point to a generalized hypothalamo-pituitary dysfunction in obesity.

Topics: Adolescent; Adrenergic alpha-Agonists; Adult; beta-Endorphin; Clonidine; Female; Growth Hormone; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Luteinizing Hormone; Metoclopramide; Naloxone; Obesity; Prolactin; Receptors, Dopamine; Receptors, Opioid

The effect of human beta-endorphin on plasma glucose, insulin, and glucagon concentrations was studied in patients with noninsulin-dependent diabetes mellitus and in normal subjects. The subjects were divided according to their body weight into lean (body mass index, less than 25) and obese (body mass index, greater than 29.5) groups. In lean subjects, infusion of 0.5 mg/h beta-endorphin caused significant increases in peripheral plasma glucose and glucagon levels, but no change in plasma insulin. In obese subjects, there was an immediate marked increase in both plasma insulin and glucagon concentrations during the beta-endorphin infusion, but the plasma glucose response was lower than that of lean subjects. In lean diabetic patients, beta-endorphin produced significant simultaneous increments in both insulin and glucagon concentrations and significantly decreased plasma glucose levels. These hormonal responses to beta-endorphin were amplified in the obese diabetic patients. There was a significant correlation (r = 0.61; P less than 0.01) between fasting plasma glucose levels and the integrated insulin area in response to beta-endorphin. The infusion of a lower dose of beta-endorphin (0.05 mg/h) in diabetic patients produced similar increments in both insulin and glucagon levels and also decreased plasma glucose concentration. These results indicate that beta-endorphin may have important glucoregulatory effects in man depending on the dose administered, the presence of obesity, and the prevailing plasma glucose concentration.

Topics: Adult; beta-Endorphin; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Endorphins; Glucagon; Humans; Hyperglycemia; Infusions, Intravenous; Middle Aged; Obesity

1. Genetically obese Zucker rats (fa/fa) contain 2-3 times higher activities mono- and diacylglycerol lipases in their spinal cords than their lean littermates. 2. When rats were exercised (1 hr daily, 5 days/week) on a treadmill for 6 months, there was a decrease of about 30% (P less than 0.05) in the activities of mono- and diacylglycerol lipases in lean rats but not in obese animals. 3. High activities of lipases in Zucker obese rats may be related to the elevated levels of beta-endorphin present in these animals. 4. The activities of arylsulfatase, beta-N-acetylhexosaminidase and alkaline phosphatase, tested to check the stability of spinal cord extracts, were similar in lean and obese rat spinal cords.

Topics: Alkaline Phosphatase; Animals; Arylsulfatases; beta-Endorphin; beta-N-Acetylhexosaminidases; Carboxylic Ester Hydrolases; Endorphins; Female; Lipoprotein Lipase; Monoacylglycerol Lipases; Obesity; Rats; Rats, Mutant Strains; Rats, Zucker; Spinal Cord

Many digestive complaints are associated with abnormalities in gastrointestinal peptide hormone function. To investigate the effect of obesity on the release of pancreatic peptide hormones, we have compared the release of insulin and glucagon in non-obese-obese Dutch women in response to isocaloric mixed meals and to Naloxone, an opioid antagonist. Healthy premenopausal women who were separated into three groups based on body mass index (BMI less than 23; 23-27, greater than 28), were fed 600-calorie breakfasts. Higher fasting levels of plasma insulin and glucagon occurred in obese (BMI greater than 28) than lean (BMI less than 23) women, while glucagon and insulin release after a high fat meal occurred in obese women. Naloxone administration in obese women decreased plasma insulin and glucagon, but in lean women, naloxone increased plasma glucagon but did not alter plasma insulin levels. Results indicate differences in opiate effects on pancreatic function in non-obese-obese women.

Topics: Adult; beta-Endorphin; Dietary Carbohydrates; Dietary Fats; Female; Food; Glucagon; Humans; Insulin; Netherlands; Obesity

Naloxone, an opiate antagonist, was given as an intravenous bolus (5 mg) in both lean and obese healthy subjects. In lean people, there was a slight trend for insulin and C-peptide concentrations to decrease below baseline values with no glucose change. Obese subjects showed an exaggerated suppression of insulin and C-peptide and a slight decrease of glucose. Glucagon was suppressed in both groups. An infusion of human beta-endorphin (0.05 mg/h) produced only minor changes in plasma glucose, insulin, glucagon, and C-peptide concentrations in lean subjects, but caused marked increments in obese. Glucagon rose in both groups, but its response was greater in obese subjects. A ten-day treatment with naloxone (1.2 mg twice a day) did not change the metabolic and hormonal responses to an oral glucose load (75 g) in lean but significantly inhibited the insulin and C-peptide responses to glucose in obese people. These results suggest that an increased opiate drive to the pancreatic beta-cell and an increased responsiveness of insulin to beta-endorphin are present in human obesity.

Topics: Adult; beta-Endorphin; Blood Glucose; C-Peptide; Female; Glucagon; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Naloxone; Obesity

In order to evaluate the origin of hyperendorphinaemia in obese patients, plasma B-endorphin (B-EP), B-lipotropin (B-LPH) and cortisol levels were measured in basal conditions and after overnight treatment with 1 mg of dexamethasone. Thirteen obese children (weight excess ranging from 44 to 100%) and 10 normal weight controls were studied. Weight gain started in prepuberty and could not be explained by concurrent diseases. Hormone levels were measured by RIA, either directly in the plasma (cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-EP and B-LPH). Basal B-EP levels in the obese children (19.4 +/- 4.9 pmol/l, mean +/- SEM) were significantly higher than in the controls (7.8 +/- 1.2, P less than 0.01), whereas B-LPH and cortisol was within normal range. In the controls, post-dexamethasone morning and afternoon hormone levels were significantly suppressed. In the obese children, B-EP concentrations remained unaffected by the treatment (14.6 +/- 5.3 and 14.9 +/- 5.2 at 08.00 and 16.00 h, respectively), whereas both B-LPH and cortisol values were significantly decreased. These data demonstrate that a short-term dexamethasone treatment is unable to correct the increased B-EP levels which characterize obese children, whereas it is effective on B-LPH and cortisol concentrations. It can be concluded that circulating B-EP in this condition loses the control of CRH. However, the origin of hyperendorphinaemia in obese patients still remains to be investigated.

Topics: Adolescent; beta-Endorphin; beta-Lipotropin; Child; Dexamethasone; Female; Humans; Hydrocortisone; Male; Obesity

In order to clarify the possible interaction between endogenous opioids and glucose homeostasis in obesity we studied Beta-Endorphin (B-Ep), ACTH, cortisol and insulin plasma levels in response to an oral glucose tolerance test (OGTT) in 8 females suffering from uncomplicated obesity and in 6 healthy volunteers of normal weight. Results were evaluated in terms of secretion areas subtracted from basal value. Basal glucose, insulin and B-Ep levels were significantly higher in the obese patients compared to controls, cortisol levels and ACTH were not statistically different between obese and normal subjects. During OGTT total areas of insulin secretion were significantly higher in the obese patients; cortisol, ACTH, B-Ep plasma levels did not change in controls, whereas obese patients showed a response to B-Ep which reached a peak at 60 minutes. The area of B-Ep response to OGTT in obese patients was significantly higher than in controls. On the basis of these results we may suggest that the opioid system belongs to the chain of neuroendocrine and metabolic events responsible for the origin and the growth of overweight. But the possibility exists that obesity itself can enhance the B-Ep secretion above all through overeating. In this regard it is to stress that glucose ingestion induces in obese patients, differently from normal subjects, insulin hypersecretion and the B-Ep secretion, possibly from gastro-enteric tract and/or pancreatic isles.

Topics: Adrenocorticotropic Hormone; Adult; beta-Endorphin; Endorphins; Female; Glucose Tolerance Test; Humans; Hydrocortisone; Insulin; Middle Aged; Obesity

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Anorexia Nervosa; beta-Endorphin; beta-Lipotropin; Corticotropin-Releasing Hormone; Endorphins; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Middle Aged; Obesity; Pituitary-Adrenal System

To study the role of opioid peptides in human obesity, plasma beta-endorphin (beta EP), beta-lipotropin (beta LPH), and cortisol resting values, circadian rhythms, and responses to hypoglycemia were studied in 6 prepubertal and 6 pubertal obese adolescents (at least 40% above ideal body weight) and in 10 normal subjects matched for age, sex, and pubertal development. Baseline plasma beta LPH and beta EP concentrations in both obese children and adolescents were twice as high as those in normal controls, while cortisol levels were not different. Cortisol, beta EP, and beta LPH levels had a clear circadian rhythmicity in all subjects, with the exception of obese pubertal boys whose plasma beta EP concentrations were constant throughout the day. After insulin administration, the fall in blood sugar was similar in all groups. Plasma cortisol and beta EP responses were similar in both obese and normal prepubertal subjects. In obese pubertal adolescents, beta EP did not increase significantly after hypoglycemia, although it did increase in normal weight pubertal subjects. In normal prepubertal subjects, the circadian rhythms of beta EP and beta LPH secretion and release induced by hypoglycemia suggest the presence of a well developed neuroendocrine control of proopiomelanocortin-related peptide secretion. In prepubertal obese children, the increased plasma beta EP and beta LPH levels with the maintenance of their circadian rhythm and responsivity to hypoglycemia suggest overactivity of anterior pituitary secretion. In obese adolescents, in spite of the normal rhythm of beta LPH and cortisol, beta EP levels did not change throughout the day, thus suggesting beta EP secretion from nonpituitary sources in these subjects. The present study indicates a possible direct role for hyperendorphinemia in the induction of overeating in obese children and adolescents.

Topics: Adolescent; Age Factors; beta-Endorphin; beta-Lipotropin; Blood Glucose; Child; Child, Preschool; Endorphins; Female; Humans; Hydrocortisone; Insulin; Male; Obesity; Puberty; Reference Values

Metabolic defects in obese (fa/fa) Zucker rats have previously been shown to be reversed by adrenalectomy; however, hypercorticosteronemia has not been demonstrated. We now report that the total daily excretion of corticosterone and urea nitrogen are significantly greater (P less than 0.01) in obese Zucker rats than in age-matched lean Zucker rats. This excessive excretion of corticosterone is not of autonomous adrenal origin, since dexamethasone treatment (20 micrograms/kg X day) for 2 days induced a proportionate reduction in corticosterone excretion (approximately 50%) in both obese and lean Zucker rats. Corticosterone excretion was further suppressed to levels not different from those in lean rats after 2 days of dexamethasone (40 micrograms/kg X day). Both the peak and total pituitary beta-endorphin secretion in response to an iv bolus of corticotropin-releasing factor (CRF) were diminished in obese Zuckers. The response to CRF in obese Zucker rats was dampened and superimposable on that of dexamethasone-treated lean Zucker rats, suggesting the existence of chronic hypercorticosteronemia as a component of this genetic obesity. These observations provide evidence for a compensatory alteration of the pituitary-adrenal axis. We suggest that corticosterone turnover may be increased in obese Zucker rats.

Topics: Animals; beta-Endorphin; Corticosterone; Corticotropin-Releasing Hormone; Dexamethasone; Endorphins; Female; Kinetics; Obesity; Pituitary Gland; Rats; Rats, Zucker

The plasma beta-endorphin of obese human subjects and non-obese controls was compared following the intravenous infusion of 25 grams of glucose. The plasma beta-endorphin of the obese subjects was significantly higher than controls one hour and four and one half hours after glucose infusion. The increased beta-endorphin of the obese subjects was associated with falling blood sugar.

Topics: Adult; beta-Endorphin; Blood Glucose; Chromatography, Affinity; Endorphins; Female; Glucose; Humans; Injections, Intravenous; Male; Middle Aged; Obesity; Radioimmunoassay; Time Factors

Topics: Adult; beta-Endorphin; Circadian Rhythm; Diet, Reducing; Endorphins; Female; Humans; Obesity

It has been hypothesized that opioid peptides play a role in the development of obesity. The opiate antagonist naltrexone decreases glucose-stimulated insulin release, while the sensitivity of diabetic rats to naloxone-induced satiety is increased. These findings suggest a possible interaction between glucose concentrations and opiate antagonists in the control of food intake. In three experiments the energy balance and glucose regulatory responses of Zucker obese and lean rats to chronic administration of nalmefene, an opiate antagonist, were measured. Nalmefene, when injected subcutaneously or added to feed for 21 days, decreased food intake and weight gain of obese and lean rats. These responses were more pronounced during the first week of treatment and were greater in obese than lean rats. Nalmefene increased glucose concentrations during day 1 and weeks 1, 2 and 3 only when given subcutaneously. Nalmefene given intragestrically attenuated glucose-stimulated increases in insulin release only in obese rats. Thus, chronic nalmefene administration is not likely to be an effective treatment for obesity or diabetes.

Topics: Administration, Oral; Animals; beta-Endorphin; Blood Glucose; Endorphins; Energy Metabolism; Feeding Behavior; Female; Injections, Subcutaneous; Insulin; Male; Naltrexone; Narcotic Antagonists; Obesity; Rats; Rats, Zucker; Tolbutamide

Eight obese patients (exceeding ideal body weight by 50% or more) with no endocrinological or metabolic disorders and 8 healthy, age-matched, normal-weight volunteers were submitted to an overnight short dexamethasone (DXM) suppression test and to a psychological assessment through various psychometric scales. Plasma B-Endorphin (B-EP), B-Lipotropin (B-LPH), ACTH and cortisol concentrations were evaluated in basal conditions, as well as 9 and 17 hours after late night administration of 1 mg DXM in both groups. All hormones were measured by radioimmunoassay, either directly in the plasma (ACTH and cortisol) or after silicic acid extraction and Sephadex G-75 column chromatography (B-LPH and B-EP). In obese patients, plasma B-EP levels in basal conditions were three times higher than in normal weight controls and remained unaltered by DXM suppression. ACTH and B-LPH, in contrast, were within the normal range and were significantly reduced by DXM. In 3 of the 8 patients, plasma cortisol concentrations at 17 hours post-DXM were greater than 50 ng/ml indicating an early escape from the suppression. Psychometric evaluations revealed a prevalence of depressive personality in obese patients. These data indicate an hypersecretion of B-EP in obese patients, which is only partially dependent on hypothalamic control.

Topics: Adrenocorticotropic Hormone; Adult; Affect; beta-Endorphin; beta-Lipotropin; Depressive Disorder; Dexamethasone; Endorphins; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Obesity; Pituitary-Adrenal System

To test the hypothesis that endogenous opiates play a role in the etiology of the sleep apnea syndrome, we administered naloxone, an opiate antagonist, to ten obese humans with sleep apnea. On two separate nights we measured the frequency and severity of sleep apnea during naloxone infusion vs saline control infusion. The number of oxyhemoglobin desaturation episodes was not significantly lowered but the average maximal oxyhemoglobin desaturation fell significantly (P less than 0.01) with naloxone. The desaturation index (average maximal oxyhemoglobin desaturation times desaturations per hour) fell by 21 percent (P less than 0.05) on the night of naloxone infusion. Nine of the ten patients had a lower desaturation index with naloxone. REM sleep decreased by 80 percent (P less than 0.05) in the subjects in whom it was measured. We conclude that opiate antagonists hold promise in the treatment of sleep apnea and that the endogenous opiate system may be involved in the production of sleep apnea.

Topics: beta-Endorphin; Endorphins; Female; Humans; Male; Naloxone; Obesity; Sleep Apnea Syndromes; Sleep, REM

Opioid peptides in the brain are postulated to mediate the hunger component of the control of food intake and regulation of body weight and concentrations are increased in the pituitaries of genetically obese rodents. However, systemic increases in opioids have been associated with satiety. Thus a chronic decrease in systemic concentrations of the opioid beta-endorphin induced by autoimmunization was predicted to increase food intake and body weight. Zucker obese (n = 20, 568 +/- 13 g) and lean (n = 20, 299 +/- 16 g) rats were autoimmunized against bovine serum albumin (BSA) or BSA conjugated to beta-endorphin (BSA-BE). Eight weeks after immunization serum from BSA-BE rats bound at least 7 times the circulating concentration of beta-endorphin. Food intakes were greater in BSA-BE obese (31.7 vs. 30.4 g/day, p less than 0.001) and lean rats (21.4 vs. 21.0 g/day, p less than 0.007) during weeks 5-8 and only obese rats, weeks 9-12 (31.8 vs. 30.3 g/day, p less than 0.009). Body weight gains were greater for BSA-BE than BSA obese rats during weeks 1-4 (1.34 vs. 0.92 g/day, p less than 0.05) and 9-12 (0.95 vs. 0.43 g/day, p less than 0.01). At 8 weeks the plasma concentrations of "free" beta-endorphin were decreased 78% (34 vs. 154 pmol/l, p less than 0.001) and "total" ("free" plus antibody-bound) beta-endorphin were increased (427 vs. 101 pmol/l, p less than 0.001). These results suggest that systemic concentrations of beta-endorphin may play an important role in the control of food intake and regulation of energy balance.

Topics: Animals; Autoantibodies; beta-Endorphin; Body Weight; Eating; Endorphins; Female; Hypothalamus; Male; Obesity; Pituitary Gland; Protein Binding; Rats; Rats, Zucker

The basal levels of beta-endorphin were measured in 43 women with various grades of hirsutism. The degree of the hair growth, weight, body mass index (BMI), age, menstrual regularity and various androgen or pituitary hormone values were not sufficient to distinguish the patients with regard to their beta-endorphin levels. In 11 patients a clinical diagnosis of a polycystic ovarian disease-like disorder was made. The beta-endorphin values of these women did not differ from those of 10 women with adrenal hyperandrogenism or the other hirsute women with identical BMI. Plasma beta-endorphin was significantly higher in obese hirsute patients with a low testosterone/sex-hormone-binding globulin (T/SHBG) ratio than in lean, nonhirsute women with a higher T/SHBG ratio (P less than 0.02). The findings suggest a possible but complex connection of beta-endorphin with some forms of female hyperandrogenism.

Topics: Adolescent; Adult; Androgens; beta-Endorphin; Body Composition; Endorphins; Female; Hirsutism; Humans; Middle Aged; Obesity; Polycystic Ovary Syndrome

Increased opiate peptide concentrations in brain and plasma have been associated with increased feeding. The role of beta-endorphin in the control of food intake and obesity was examined by measuring concentrations in hypothalamus, pituitary and plasma of hungry (6-hr fasted) and satiated (5 min after a meal) Zucker obese and lean rats. beta-Endorphin concentrations (1) in satiated vs. hungry rats were increased in the VMH (90 vs. 79 pg/mg tissue, p less than 0.05) and decreased in the supraoptic nucleus (65 vs. 78 pg/mg tissue, p less than 0.05), (2) in obese vs. lean rats were decreased in the VMH (79 vs. 90 pg/mg tissue, p less than 0.05) and (3) in female vs. male rats were increased in the anterior hypothalamus (123 vs. 59 pg/mg tissue, p less than 0.01) and VMH (90 vs. 79 pg/mg tissue, p less than 0.05). Analysis of a phenotype by feeding condition interaction revealed that obese but not lean rats had higher beta-endorphin concentrations in the satiated vs. hunger condition. However, plasma beta-endorphin concentrations did not differ with feeding condition, phenotype or sex. Intermediate and posterior but not anterior pituitary beta-endorphin concentrations were lower in obese than lean rats. Thus, there is some evidence for a relationship between beta-endorphin concentration and feeding in the hypothalamus, but beta-endorphin concentrations in plasma do not appear to be influenced by feeding condition or obesity.

Topics: Animals; beta-Endorphin; Endorphins; Feeding Behavior; Female; Hunger; Hypothalamus; Male; Obesity; Pituitary Gland; Radioimmunoassay; Rats; Rats, Zucker; Satiety Response; Sex Characteristics

Obesity as a common disorder of lipid metabolism might be caused by defective hypothalamic control as demonstrated by ventromedial lesions or the effect of cholecystokinin application. The hypothalamic proopiomelanocorticotropin is the precursor of hormonal fragments affecting fat mobilisation, the endocrine pancreas and gastrointestinal functions.

Topics: Animals; beta-Endorphin; Cholecystokinin; Eating; Endorphins; Glucagon; Humans; Hypothalamic Diseases; Insulin; Intestinal Absorption; Lipid Mobilization; Lipids; Lipolysis; Obesity; Pro-Opiomelanocortin; Receptors, Opioid; Satiety Response; Vagus Nerve

Young and mature, genetically obese and non-obese, spontaneously hypertensive rats (SHR) were injected with saline (controls) or naloxone for 12 weeks. Naloxone stilled the hyperphagia to a normal intake in the obese SHR (Obese/SHR) so that young Obese/SHR did not develop their usual massive obesity and mature Obese/SHR that had become massively obese were reduced to leanness. The naloxone-treated young, obese and non-obese SHR (controls) exhibited marked reduction of the weight of their pituitary and adrenal glands, whereas the pituitary and adrenal glands of naloxone-treated mature, obese and non-obese/SHR were greatly increased in weight. The elevated systolic blood pressure of the obese and non-obese rats was reduced after chronic treatment with naloxone. Naloxone treatment caused reduction of blood ACTH, corticosterone, and beta endorphin levels but elevated growth hormone levels. The characteristic hyperinsulinemia, hyperlipidemia, hyperglycemia, elevated BUN levels, and the Cushingoid spectrum of degenerative changes found in Obese/SHR did not appear in naloxone-treated rats.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Pressure; Body Weight; Corticosterone; Cushing Syndrome; Disease Models, Animal; Endorphins; Female; Growth Hormone; Male; Naloxone; Obesity; Organ Size; Pituitary Gland; Rats; Rats, Inbred SHR; Rats, Inbred Strains

Topics: Adult; beta-Endorphin; Endorphins; Female; Glucagon; Humans; Hydrocortisone; Obesity; Physical Exertion

Topics: Adrenocorticotropic Hormone; beta-Endorphin; Endorphins; Female; Humans; Hydrocortisone; Male; Nalorphine; Obesity; Prolactin; Radioimmunoassay; Thyrotropin; Time Factors

Following the oral administration of 100 g of glucose, morbidly-obese subjects and non-obese controls demonstrated increased levels of plasma immunoreactive beta-endorphin. There was a slow rise in plasma immunoreactive beta-endorphin in the non-obese controls throughout the 3-h observation period. The obese subjects demonstrated a delayed and significantly greater rise of plasma immunoreactive beta-endorphin, when compared to the controls. These findings may have implications for further research in human obesity.

Topics: Adult; beta-Endorphin; Blood Glucose; Endorphins; Female; Glucose; Humans; Kinetics; Male; Obesity

Male and female, young (2 months old) and mature (10 months old), obese and nonobese, spontaneously hypertensive rats (SHR) were treated with dexamethasone, 5 micrograms/rat and 10 micrograms/rat, respectively, subcutaneously (SC) 2 times daily for 5 months. Steroid treatment stilled the voracious appetite of the obese SHR, and the massively obese, mature animals were reduced to almost normal size. The young, steroid-treated, obese SHR did not develop their genetically programmed corpulency. The untreated, young and mature, obese SHR ate voraciously, became massively obese, and developed their characteristic Cushing's disease-like spectrum of degenerative changes, eg, hypertension, hyperlipidemia, hyperglycemia, muscle wasting, kidney stones, thin skin, and accelerated aging. The blood pressure of the steroid-treated animals was lowered concomitant with reduced levels of circulating ACTH, beta endorphin, insulin, triglycerides, and cholesterol. Dexamethasone caused hyperlipidemia, hyperglycemia, and increased BUN levels in young obese and nonobese SHR only. The mature obese SHR had giant-sized thymus glands that were further enlarged with steroid treatment; dexamethasone was thymolytic in young, obese and nonobese SHR. Dexamethasone caused severe reduction of pituitary and adrenal gland size, simulating the condition of hypophysectomy. These findings demonstrate that dexamethasone suppression of the pituitary-adrenal axis palliates and prevents the spontaneous development of Cushingoid degenerative changes in these genetically obese and hypertensive rats.

Topics: Adrenal Glands; Adrenocorticotropic Hormone; Animals; beta-Endorphin; Blood Glucose; Blood Urea Nitrogen; Cushing Syndrome; Dexamethasone; Disease Models, Animal; Endorphins; Female; Hypertension; Insulin; Lipids; Male; Obesity; Organ Size; Pituitary Gland; Rats; Rats, Inbred Strains

Topics: Animals; beta-Endorphin; Blood Glucose; Duodenum; Endorphins; Female; Hypothalamus, Middle; Obesity; Pancreas; Pituitary Gland; Radioimmunoassay; Rats; Rats, Inbred Strains

Plasma opioid levels were determined in 9 obese non-diabetic subjects, their 8 age matched controls, and in 29 diabetic patients; 10 maintained on diet alone, 6 on an oral hypoglycemic agent (chlorpropamide) and 13 treated with insulin. Five age matched controls for the diabetic groups were also studied for comparison. beta-endorphin and met-enkephalin levels were measured by radioimmunoassay. Enkephalin-like activity was measured by a receptor assay. Among the study groups, diabetic patients receiving insulin showed a 64% elevation of plasma beta-endorphins and diabetic patients on chlorpropamide showed a 121% increase in enkephalin-like activity. There were no statistically significant differences in the plasma met-enkephalin values in the treatment groups though levels were decreased (p less than 0.05) in diabetics vs non-diabetics. The pathophysiological importance of these alterations remains to be elucidated.

Topics: beta-Endorphin; Chlorpropamide; Diabetes Mellitus; Diet, Diabetic; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Humans; Insulin; Obesity; Radioimmunoassay; Radioligand Assay; Reference Values

The association of acanthosis nigricans with pituitary tumors and insulin-resistant diabetes suggests that a pituitary peptide may promote papillomatosis and acanthosis characteristic of acanthosis nigricans. Although such a peptide has not been isolated, it may derive by sequential cleavage from the 31,000-dalton precursor peptide to ACTH and beta-lipotropin (beta-LPH). In order to evaluate the role of pituitary peptides in the pathogenesis of acanthosis nigricans, we compared plasma levels of beta-endorphin (beta-EP) and ACTH in plasma of 8 fasting patients with obesity-associated benign acanthosis nigricans and 7 fasting normal controls utilizing sensitive radioimmunoassay procedures. Mean plasma beta-EP levels for the acanthosis nigricans and control subjects were not significantly different (90 pg/ml vs. 140 pg/ml), nor was any significant difference observed between plasma ACTH levels of the 2 groups (42.3 and 31.2 pg/ml, respectively.) Our data indicate that plasma levels of the pituitary-derived peptides ACTH and beta-EP are not increased in obesity-associated benign acanthosis nigricans, and suggest that its proposed hormonal mediator might originate independently from the large peptide precursor of ACTH, beta-LPH and their fragments.

Topics: Acanthosis Nigricans; Adolescent; Adrenocorticotropic Hormone; Adult; beta-Endorphin; Child; Endorphins; Humans; Middle Aged; Obesity; Pituitary Gland; Reference Values

Topics: Anorexia Nervosa; beta-Endorphin; Endorphins; Female; Humans; Hypoglycemia; Male; Obesity; Physical Exertion

Topics: Adolescent; Adult; beta-Endorphin; Cushing Syndrome; Endorphins; Humans; Lipoproteins, LDL; Middle Aged; Obesity; Radioimmunoassay

The role of beta-endorphin in the development of several obesity syndromes was examined. Adult female hooded rats received ventromedial hypothalamic lesions, dorsolateral tegmental lesions, parasagittal hypothalamic knife cuts, intraventricular 5,7-dihydroxytryptamine, ovariectomy, control surgery, or were deprived to 75% of normal body weight. Dose-dependent suppression of food intake by the opiate antagonist naloxone (0.5, 1.8, 6.8, or 25.0 mg/kg, ip) was measured during once-daily 4-h food access periods. No difference was found among the groups at any dose. Pituitary beta-endorphinlike immunoreactivity (BELI) was substantially decreased in knife-cut rats, but was unaltered by other treatments. Obesity had no effect on BELI. In another experiment, rats made obese by prolonged maintenance on palatable foods had elevated pituitary BELI levels. Feeding mechanisms involving opioid peptides do not appear to be of etiological significance in the syndromes examined.

Topics: 5,7-Dihydroxytryptamine; Animals; beta-Endorphin; Castration; Endorphins; Feeding Behavior; Female; Hypothalamus; Naloxone; Obesity; Pituitary Gland; Rats

Naltrexone, an opiate antagonist, was administered to young obese (ob/ob) and lean mice for five weeks. Animals had continuous access to food and received 10 mg/kg SC twice daily with equivalent volumes of saline given to controls. The effects on body weight, and pituitary and plasma levels of beta-endorphin-like material were measured. Naltrexone-injected obese animals gained weight more slowly over the first three weeks while the weight gain of lean animals was not affected by naltrexone. Plasma levels of beta-endorphin were shown to be significantly higher in untreated ob/ob mice and this difference increased with age (4-20 weeks). With naltrexone treatment, plasma levels in +/? mice rose and exceeded those in ob/ob. Saline treatment appeared to be a stress, and pituitary beta-endorphins rose 4-6 fold in ob/ob compared with +/?. While naltrexone reduced the levels of ob/ob pituitary towards normal, no effect on beta-endorphin levels in pituitary of lean mice was obtained. In vitro studies of effects of the opiate antagonists, naloxone, on insulin secretion by isolated islets provided additional evidence of resistance of lean mice to naloxone relative to ob/ob. (IRI secretion fell only in naloxone treated ob/ob islets). These observations support the contention that this form of genetic obesity is characterized by elevated endogenous opiate levels and an increased sensitivity to opiate antagonists such as naltrexone or naloxone.

Topics: Animals; beta-Endorphin; Body Weight; Endorphins; Insulin; Insulin Secretion; Islets of Langerhans; Mice; Mice, Obese; Naloxone; Naltrexone; Obesity; Pituitary Gland; Receptors, Opioid