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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Batterham et al. report that the gut peptide hormone PYY3-36 decreases food intake and body-weight gain in rodents, a discovery that has been heralded as potentially offering a new therapy for obesity. However, we have been unable to replicate their results. Although the reasons for this discrepancy remain undetermined, an effective anti-obesity drug ultimately must produce its effects across a range of situations. The fact that the findings of Batterham et al. cannot easily be replicated calls into question the potential value of an anti-obesity approach that is based on administration of PYY3-36.
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PMID:Physiology: does gut hormone PYY3-36 decrease food intake in rodents? 1216 64

There is compelling evidence that patients with schizophrenia are prone to gain weight. In addition, atypical antipsychotic (AAP) drugs also induce weight gain. All antipsychotic drugs produce weight gain but the potential varies. Many studies overwhelmingly confirm that AAP drugs produce substantially more weight gain in comparison to conventional antipsychotic drugs. Clozapine and olanzapine have the most weight inducing potential. Even ziprasidone, which is considered to be weight neutral, and aripiprazole a dopamine modulator produce weight gain in some. The pathophysiology of weight gain is complicated. Many neurohormones, neuropeptides, gut hormones, as well as adipose tissue and hair root derived hormones interact with environmental factors to produce weight gain. Management of weight gain is a difficult problem. Basic to treatment is an understanding of the etiology. Drug induced obesity provides a unique opportunity to psychiatrists to understand this clinically important problem. In the absence of this knowledge, prevention is the best hope. Education, diet control and simple behavioral measures may prevent excessive weight gain. In those with weight gain, treatment can be attempted with pharmacotherapy with careful monitoring of the side effects.
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PMID:Atypical antipsychotic induced weight gain: pathophysiology and management. 1532 1

Ghrelin, a gut-brain peptide that signals hunger, is normally suppressed after meals. Subnormal suppression of postprandial ghrelin, previously noted in obese, insulin-resistant individuals, may contribute to increased food intake. Given the ethnic disparities in obesity and obesity-related cardiovascular morbidity in the United States, the present study compared a single postprandial ghrelin measure in 43 women (22 white, 21 black). Each completed a rigorously controlled 4-d dietary intervention designed to maintain weight and constant daily sodium and potassium intake (220 mEq Na, 40 mEq K). Two hours after consuming a test meal of identical content, blood samples were drawn to assess postprandial ghrelin, leptin, and norepinephrine; resting cardiovascular function was measured; and a 24-h urinary cortisol sample was obtained. Independent of body mass index, postprandial ghrelin was significantly higher in black vs. white women, and higher ghrelin was associated with higher cortisol in blacks, who failed to show the expected inverse relation between ghrelin and central obesity seen in whites. Higher ghrelin was correlated with higher blood pressure but lower norepinephrine in obese women. These findings suggest subnormal postprandial ghrelin suppression (or faster ghrelin rebound) in black women, especially the obese, that might play a role in their increased prevalence of obesity and cardiovascular disorders.
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PMID:Postprandial ghrelin is elevated in black compared with white women. 1535 47

Obesity is the main cause of premature death in the UK. Worldwide its prevalence is accelerating. It has been hypothesized that a gut nutriment sensor signals to appetite centres in the brain to reduce food intake after meals. Gut hormones have been identified as an important mechanism for this. Ghrelin stimulates, and glucagon like peptide-1, oxyntomodulin, peptide YY (PYY), cholecystokinin and pancreatic polypeptide inhibit, appetite. At physiological postprandial concentrations they can alter food intake markedly in humans and rodents. In addition, in obese humans fasting levels of PYY are suppressed and postprandial release is reduced. Administration of gut hormones might provide a novel and physiological approach in anti-obesity therapy. Here, we summarize some of the recent advances in this field.
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PMID:Gut hormones and the control of appetite. 1535 78

Ghrelin, a brain-gut peptide discovered from the stomach, stimulates growth hormone release, food intake, adiposity, and weight gain. Circulating ghrelin levels are modulated under conditions of positive and negative energy balance, however its effect on macronutrient selection is not known. The present experiment investigates the effect of ghrelin on single and two-diet feeding paradigms in high-carbohydrate (HC) and high-fat (HF) preferring rats. In the macronutrient selection test in which rats were given free access to either high-carbohydrate or high-fat diet, an intracerebroventricular (i.c.v.) administration of ghrelin potently enhanced fat intake over carbohydrate intake in both HC- and HF-preferring rats. In the diet preference test in which rats were given free access to both high-carbohydrate and high-fat diets simultaneously, an i.c.v. administration of ghrelin also preferentially enhanced fat consumption over carbohydrate in both HF- and HC-preferring rats. Intracerebroventricular administrations of galanin and neuropeptide Y enhanced fat and carbohydrate ingestion, respectively. Centrally administered ghrelin enhanced fat ingestion. These results provide further insights for the role of ghrelin in feeding behavior and the development of obesity.
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PMID:Central administration of ghrelin preferentially enhances fat ingestion. 1538 Mar 11

Adult aging in humans is associated with marked and sustained increases in sympathetic nervous system (SNS) activity to several peripheral tissues, including the heart, the gut-liver circulation, and skeletal muscle. This chronic activation of the peripheral SNS likely is, at least in part, a primary response of the central nervous system to stimulate thermogenesis to prevent further fat storage in the face of increasing adiposity with aging. However, as has been proposed in obesity hypertension, this tonic activation of the peripheral SNS has a number of adverse secondary cardiovascular consequences. These include chronic reductions in leg blood flow and vascular conductance, increased tonic support of arterial blood pressure, reduced limb and systemic alpha-adrenergic vasoconstrictor responsiveness, impaired baroreflex buffering, large conduit artery hypertrophy, and decreased vascular and cardiac responsiveness to beta-adrenergic stimulation. These effects of chronic age-associated SNS activation on the structure and function of the cardiovascular system, in turn, may have important implications for the maintenance of physiological function and homeostasis, as well as the risk of developing clinical cardiovascular and metabolic diseases in middle-aged and older adults.
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PMID:Collateral damage: cardiovascular consequences of chronic sympathetic activation with human aging. 1547 26

Obesity has long been considered a behavioral disorder. Recent breakthroughs in our understanding of body weight regulation, however, have shown that once adipose tissue accumulates, a system of overlapping neuroendocrine systems actively resists weight loss. This counter-regulatory mechanism, which has evolved as protection against starvation, causes changes in appetite and metabolism that limit the amount of weight lost with every obesity intervention, including surgery. Future therapies for obesity will focus on neutralizing the counter-regulatory mechanisms in a coordinated manner, making greater weight losses possible. At this point, gastric stimulation appears to play a role in suppressing the compensatory mechanisms of the gut. Thus, gastric stimulation should work best when combined with other treatments such as diet, exercise, and behavioral change.
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PMID:Gastric pacing is not enough: additional measures for an effective obesity treatment program. 1547 86

New therapeutic targets for noncognitive reductions in energy intake, absorption, or storage are crucial given the worldwide epidemic of obesity. The gut microbial community (microbiota) is essential for processing dietary polysaccharides. We found that conventionalization of adult germ-free (GF) C57BL/6 mice with a normal microbiota harvested from the distal intestine (cecum) of conventionally raised animals produces a 60% increase in body fat content and insulin resistance within 14 days despite reduced food intake. Studies of GF and conventionalized mice revealed that the microbiota promotes absorption of monosaccharides from the gut lumen, with resulting induction of de novo hepatic lipogenesis. Fasting-induced adipocyte factor (Fiaf), a member of the angiopoietin-like family of proteins, is selectively suppressed in the intestinal epithelium of normal mice by conventionalization. Analysis of GF and conventionalized, normal and Fiaf knockout mice established that Fiaf is a circulating lipoprotein lipase inhibitor and that its suppression is essential for the microbiota-induced deposition of triglycerides in adipocytes. Studies of Rag1-/- animals indicate that these host responses do not require mature lymphocytes. Our findings suggest that the gut microbiota is an important environmental factor that affects energy harvest from the diet and energy storage in the host. Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AY 667702--AY 668946).
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PMID:The gut microbiota as an environmental factor that regulates fat storage. 1550 15

Peptide YY (PYY) is an important gut hormone synthesized and secreted by the gastrointestinal tract. Peripheral administration of PYY(3-36), one of the circulating forms of PYY, is known to inhibit food intake. This anorexigenic effect is masked by stress inhibition of appetite, and it is therefore important for animals to be thoroughly acclimatised for PYY(3-36) to be effective. Evidence suggests that PYY(3-36) acts via the hypothalamic Y(2) receptor. Levels of the anorexigenic hormone PYY(3-36) are low in overweight volunteers and could provide an important therapeutic avenue in the quest to combat the obesity epidemic.
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PMID:Peptide YY and appetite control. 1552 48

Increased food intake is a major factor in the development of obesity, and the control of meal size is a valid approach to reduce food intake in humans. Meal termination, or satiety, is thought to be organized within the caudal brainstem where direct signals from the food handling alimentary canal and long-term signals from the forebrain converge in the solitary nucleus. Cholecystokinin (CCK) released from the gut after ingestion of food has been strongly implicated in nucleus tractus solitarius (NTS)-mediated satiation, but the exact cellular and intracellular signaling events are not understood. Using Western blotting and immunohistochemistry with phosphospecific antibodies, we demonstrate here that peripheral administration of CCK in rats leads to rapid activation of the extracellular signal-regulated kinase (ERK) signaling cascade in NTS neurons and that blockade of ERK signaling with microinfusion of a selective mitogen-activated ERK kinase inhibitor into the fourth ventricle attenuates the capacity of CCK to suppress food intake. In addition, we show that CCK-induced activation of ERK results in phosphorylation of the voltage-dependent potassium channel Kv4.2 and the nuclear transcription factor CREB (cAMP response element-binding protein). The results demonstrate that ERK signaling is necessary for exogenous CCK to suppress food intake in deprived rats and suggest that this pathway may also be involved in natural satiation and the period of satiety between meals through coupling of ERK activation to both cytosolic and nuclear effector mechanisms that have the potential to confer acute and long-term changes in neuronal functioning.
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PMID:Extracellular signal-regulated kinase 1/2 signaling pathway in solitary nucleus mediates cholecystokinin-induced suppression of food intake in rats. 1553 96


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