Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucagon and insulin were measured by heterologous immunoassays in plasma samples of 17 garden warblers (Sylvia borin) kept under constant ad libitum or fasting-refeeding conditions during the migratory season from September to May. Plasma levels of key metabolic indicators (glucose, triglycerides, cholesterol, and free fatty acids) were measured every 2 weeks. Measurements of the two hormones concur with the general assumption of a higher glucagon:insulin ratio, indicating a more pronounced catabolism in birds than in mammals. The concentrations of both hormones varied (insulin: 0.7-7.7 microIU/ml, n = 66; glucagon: 0.4-4.5 ng/ml, n = 99), but differences between mean values per month were significant only for glucagon. Neither hormone titer correlated with either the seasonal or a fasting-refeeding-induced body mass cycle. However, there was a positive correlation between food intake, changes in body mass, and plasma triglycerides and insulin; in contrast, there was a negative relationship with the glucagon:insulin ratio. Glucagon showed only a small negative relationship to plasma glucose and cholesterol, but correlated directly more closely with plasma free fatty acids. The present data support the fact that glucagon is more lypolytic in birds than in mammals. Pancreatic hormones are suggested to participate in the regulation of premigratory hyperphagia and hyperlipemia.
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PMID:A role for pancreatic hormones in the regulation of autumnal fat deposition of the garden warbler (Sylvia borin)? 924 24

Hypothalamic neuronal histamine and its H(1) receptor (H(1)-R), a leptin signaling pathway in the brain, regulate body weight and adiposity by affecting food intake and energy expenditure. Glucagon-like peptide-1 and/or corticotrophin-releasing hormone mediate leptin signaling to neuronal histamine. Leptin-induced suppression of food intake and upregulation of uncoupling protein-1 expression in brown adipose tissue were partially attenuated in histamine H(1)-R knockout (H(1)KO) mice. H(1)KO mice developed maturity-onset obesity. Hyperphagia and decreased energy expenditure assessed by the expression of uncoupling protein-1 mRNA were observed in older (48-wk-old) obese H(1)KO mice but not in younger (12-wk-old) non-obese H(1)KO mice. However, the diurnal feeding rhythm was impaired even in younger non-obese animals. Specifically, disruption of the feeding rhythm developed before the onset of obesity in H(1)KO mice. Correction of these abnormal feeding rhythms with scheduled feeding improved the obesity and associated metabolic disorders in the H(1)KO mice. These findings suggest that histamine H(1)-R is crucial for regulating the feeding rhythm and in mediating the effects of leptin. Early disruption of H(1)-R-mediated functions in H(1)KO mice may lead to hyperphagia and decreased energy expenditure, which may contribute to the development of obesity in these animals.
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PMID:Hypothalamic neuronal histamine regulates body weight through the modulation of diurnal feeding rhythm. 1872 79

Gastrointestinal mechanisms involved in the suppression of appetite are compromised in obesity. Glucagon-like peptide-1 (GLP-1) is released in response to nutrients, suppresses food intake, and has been shown to play a role in regulation of energy balance. It is not known whether obese-prone (OP) rats exhibit dysfunctional GLP-1 signaling that could contribute to decreased nutrient-induced satiation and hyperphagia. Therefore, we examined the effects of exogenous intraperitoneal administration of the GLP-1R agonist, exendin-4 (Ex-4), on food intake in OP and obese-resistant (OR) rats during chow or high-energy/high-fat (HE/HF) feeding. All doses of Ex-4 effectively suppressed intake in OP and OR rats fed chow; however, during HE/HF-feeding, OP rats suppressed intake significantly less than OR rats at all Ex-4 doses tested. This was associated with downregulation of GLP-1R mRNA expression in the vagal nodose ganglia of OP rats. Furthermore, HE/HF-fed OP rats had significantly lower plasma GLP-1 levels, decreased protein levels of GLP-1 in the intestinal epithelium, and reduced number of L cells in the distal ileum. These results demonstrate that HE/HF-feeding, coupled with OP phenotype, results in reduced endogenous GLP-1 and GLP-1R activation, indicating that impaired GLP-1 signaling during obesity may exacerbate hyperphagia and weight gain.
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PMID:Combination of obesity and high-fat feeding diminishes sensitivity to GLP-1R agonist exendin-4. 2342 71

Hypothalamic hyperphagia and obesity are characterized by a lack of satiety and an abnormally high appetite that is difficult to control. We herein report the cases of two patients with hypothalamic hyperphagia and obesity with MRI-detectable hypothalamic lesions. These patients suffered from diabetes mellitus associated with an abnormal eating behavior and weight gain. Liraglutide was successfully used to treat their diabetes mellitus and suppress their abnormal appetites. Glucagon-like peptide-1 analogues, including liraglutide, are promising treatment options in patients with hypothalamic hyperphagia and obesity, as these agents enhance the hypothalamic input of the satiety signal, which is lacking in such patients.
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PMID:Liraglutide as a potentially useful agent for regulating appetite in diabetic patients with hypothalamic hyperphagia and obesity. 2513 Jan 12

Lean and obese Zucker rats were deprived of food for 12, 24, and 48 h. After sacrifice, plasma and brain tissue were saved for hormone and regional hypothalamic monoamine analysis. An ad libitum group was killed at time 0 for comparison to the food deprived groups. Insulin (I), C-peptide (CP), glucose, and the CP/I ratio were dramatically different across phenotype. Glucagon was only different at 12 h of caloric deprivation. Insulin secretion dropped substantially with fasting as reflected by the decrease in C-peptide plasma levels in both lean and obese rats. The CP/I ratio, which indicates clearance of insulin, increased in lean rats across time of fasting but did not significantly change in obese rats. Several distinct changes occurred between phenotypes in the hypothalamus across food deprivation. Lateral hypothalamic 5HT content and 5HT turnover (5HIAA/5HT) increased in lean but not obese rats during the period of fasting. Likewise ventromedial hypothalamic dopamine turnover (NE/DA) decreased during caloric deprivation in lean rats but not in the obese rats. This same turnover was increased in the PVNA of obese but not lean rats during caloric deprivation. Individual measurements of both C-peptide and insulin correlated significantly with LH 5HT turnover and VMH dopamine turnover in lean rats but not obese rats. These data suggest that obese rat's hypothalami may possibly be insensitive to insulin or some factor such as leptin that insulin may regulate. Because obese rats cannot change their levels of hypothalamic neurotransmitters when insulin or some other insulin induced factor changes, may suggest clues as to why these rats became obese. Perhaps these data may help explain the altered body weight set-point, increased adiposity, and hyperphagia in these animals.
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PMID:Neurochemical and Hormonal Changes in Lean and Obese Zucker Rats During 48 Hours of Calorie Deprivation. Are They related? 2740 98

Overeating and arrhythmic feeding promote obesity and diabetes. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs but their use is limited by side effects. Here we show that oral administration of the non-calorie sweetener, rare sugar D-allulose (D-psicose), induces GLP-1 release, activates vagal afferent signaling, reduces food intake and promotes glucose tolerance in healthy and obese-diabetic animal models. Subchronic D-allulose administered at the light period (LP) onset ameliorates LP-specific hyperphagia, visceral obesity, and glucose intolerance. These effects are blunted by vagotomy or pharmacological GLP-1R blockade, and by genetic inactivation of GLP-1R signaling in whole body or selectively in vagal afferents. Our results identify D-allulose as prominent GLP-1 releaser that acts via vagal afferents to restrict feeding and hyperglycemia. Furthermore, when administered in a time-specific manner, chronic D-allulose corrects arrhythmic overeating, obesity and diabetes, suggesting that chronotherapeutic modulation of vagal afferent GLP-1R signaling may aid in treating metabolic disorders.
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PMID:GLP-1 release and vagal afferent activation mediate the beneficial metabolic and chronotherapeutic effects of D-allulose. 2931 23

Binge eating, eating an abnormally large amount of food in a discrete period of time with a sense of loss of control over eating, is a defining feature of the eating disorders binge eating disorder (BED) and bulimia nervosa (BN). Both BED and BN are important public health problems for which there are few medical treatments. However, almost all drugs with central nervous system-mediated weight loss properties studied thus far in randomized, placebo-controlled trials in persons with BED or BN have been efficacious for reducing binge eating behavior. Glucagon-like peptide-1 (GLP-1) receptor agonists, marketed for type 2 diabetes and chronic weight management, produce weight loss in a dose dependent manner and have favorable psychiatric adverse event profiles. We hypothesize that GLP-1 receptor agonists will safely reduce binge eating behavior in individuals with BED or BN, including those with co-occurring psychiatric disorders, and propose that randomized, placebo-controlled clinical trials of GLP-1 receptor agonists be conducted in persons with BED and those with BN. To support this hypothesis, we review studies of GLP-1 and GLP-1 receptor agonists in preclinical models of binge eating, studies of GLP-1 levels in individuals with BED or BN, and preliminary data of GLP-1 receptor agonists in humans with abnormal eating behavior.
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PMID:Would glucagon-like peptide-1 receptor agonists have efficacy in binge eating disorder and bulimia nervosa? A review of the current literature. 2940 5

Background: Thymoquinone (TQ) is a safe nutrient isolated from the seeds or volatile oil extract of Nigella sativa. In addition to its benefits in glucose regulation, TQ improves feeding disorders in diabetic animals. Glucagon-like peptide-1 (GLP-1) analogs improve glycemic control and ameliorate obesity or hyperphagia. Therefore, the present study aimed to investigate the role of GLP-1 in TQ-induced anorexia. Method: Type 2 diabetes was induced in rats by nicotinamide and streptozotocin injection. TQ was orally administered to diabetic rats at different doses for 45 days. Following TQ treatment, changes in serum glucose levels, GLP-1 concentration, body weight, food intake, and water intake were determined. To further explore the interaction between GLP-1 and TQ, the inhibitor of dipeptidyl peptidase 4, sitagliptin and the GLP-1 receptor antagonist exendin 9-39 (Ex 9-39) were separately administered to TQ- or vehicle-treated diabetic rats. Results: TQ treatment attenuated hyperglycemia and reduced hyperphagy and water intake in streptozotocin-induced diabetic rats in a dose-dependent manner. Moreover, TQ treatment elevated plasma GLP-1 levels compared to those in control rats. The effects of TQ were enhanced by treatment with sitagliptin and reduced by the injection of Ex 9-39 into the brain. In contrast, similar treatment with another antioxidant (either ascorbic acid or N-acetylcysteine) produced the same anorexic effect as TQ without changing the plasma GLP-1 levels in diabetic rats. Therefore, TQ attenuated hyperphagy while increasing plasma GLP-1 levels and had antioxidant-like effects. Conclusion: TQ increased endogenous GLP-1 levels to reduce hyperphagy in diabetic rats.
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PMID:GLP-1 mediates the modulating effect of thymoquinone on feeding behaviors in diabetic rats. 3135 23