beta-endorphin and Hyperphagia

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

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

NOR1, Nur77 and Nurr1 are orphan nuclear receptors and members of the NR4A subfamily. Here, we report that the expression of hypothalamic NOR1 was remarkably decreased in mildly obese beta-endorphin-deficient mice and obese db/db mice with the leptin receptor mutation, compared with age-matched wild-type mice, whereas there were no genotypic differences in the expression of hypothalamic Nur77 or Nurr1 in these animals. The injection of NOR1 siRNA oligonucleotide into the third cerebral ventricle significantly suppressed food intake and body weight in mice. On the other hand, the decreases in hypothalamic NOR1 expression were not found in non-obese 5-HT2C receptor-deficient mice. Moreover, systemic administration of m-chlorophenylpiperazine (mCPP), a 5-HT2C/1B receptor agonist, had no effect on hypothalamic NOR1 expression, while suppressing food intake in beta-endorphin-deficient mice. These findings suggest that 5-HT2C receptor-independent proopiomelanocortin-derived peptides regulate the expression of hypothalamic NOR1, which is a novel modulator of feeding behavior and energy balance.

Topics: Animals; beta-Endorphin; DNA-Binding Proteins; Eating; Energy Metabolism; Hyperphagia; Hypothalamus; Male; Mice; Mice, Mutant Strains; Nerve Tissue Proteins; Nuclear Receptor Subfamily 4, Group A, Member 1; Nuclear Receptor Subfamily 4, Group A, Member 2; Piperazines; Pro-Opiomelanocortin; Receptor, Serotonin, 5-HT2C; Receptors, Steroid; Receptors, Thyroid Hormone; RNA, Small Interfering; Serotonin 5-HT2 Receptor Agonists; Serotonin Receptor Agonists; Transcription Factors

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

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

Topics: beta-Endorphin; Energy Intake; Female; Humans; Hyperphagia; Premenstrual Syndrome

The plasma beta-endorphin response to glucose ingestion was compared in 8 bulimics and 8 controls. The bulimics demonstrated a sustained elevation of plasma beta-endorphin unrelated to glucose ingestion throughout the 5-hour study period. It is hypothesized that such an elevation of beta-endorphin is the result of stress and that it may play an important role in the perpetuation of the binge-vomiting cycle.

Topics: Adolescent; Adult; beta-Endorphin; Blood Glucose; Dietary Carbohydrates; Endorphins; Feeding and Eating Disorders; Female; Humans; Hyperphagia; Radioimmunoassay

To study the possible role of plasma beta-endorphin in bulimia, we measured plasma beta-endorphin immunoreactivity in 34 female patients with normal-weight bulimia and 34 normal female controls matched for weight as percent of ideal. Plasma beta-endorphin immunoreactivity in bulimics (mean 59.6 pg/ml; SEM 5.6) was significantly lower (p less than 0.05) than in controls (mean 79.5 pg/ml; SEM 8.5). Within the bulimic group, plasma beta-endorphin immunoreactivity correlated inversely with severity of bulimic symptomatology as measured by the Eating Attitudes Test Bulimia Subscale (p less than 0.05). Endorphin level did not correlate with severity of depression or with percent ideal body weight. Abnormalities in opioid metabolism may be implicated in eating disorders and account for the addictive properties of these disorders.

Topics: Adult; beta-Endorphin; Depression; Endorphins; Feeding and Eating Disorders; Feeding Behavior; Female; Humans; Hyperphagia; Psychological Tests; Radioimmunoassay

The relationship between premenstrual tension syndrome and dietary intake was studied in a population of 20 young adult women. Caloric intake was measured during the 10 days preceding and following the menstrual cycle. Those women with more severe symptoms recorded a greater increase in caloric intake. Caloric intake during the premenstrual period also increased with age. It is hypothesized that this caloric intake may be due to increased beta-endorphin levels.

Topics: Adult; Age Factors; beta-Endorphin; Endorphins; Energy Intake; Feeding and Eating Disorders; Female; Humans; Hyperphagia; Premenstrual Syndrome

Two experimental situations induce hyperphagia in the rat: the cafeteria model and the tail-pinching model. In non-deprived rats which are offered for one hour a choice of 3 liquid cafeteria items in addition to ordinary chow and water, mild tail-pinching results in a preferential sucrose hyperphagia; naltrexone (2.5 mg/kg IP) suppresses this stress-induced hyperphagia; beta-endorphin (3 micrograms ICV) has the same effect. This apparent discrepancy is discussed: the antagonist may suppress the hyperphagia because it suppresses the reward provoked by the sucrose, the agonist because it makes it unnecessary.

Topics: Animals; beta-Endorphin; Endorphins; Feeding and Eating Disorders; Food; Food Preferences; Humans; Hyperphagia; Male; Naltrexone; Nociceptors; Rats; Rats, Inbred Strains; Stress, Psychological; Sucrose