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

Medium chain fatty acids (MCFA) are readily oxidized in the liver. Animal and human studies have shown that the fast rate of oxidation of MCFA leads to greater energy expenditure (EE). Most animal studies have also demonstrated that the greater EE with MCFA relative to long-chain fatty acids (LCFA) results in less body weight gain and decreased size of fat depots after several months of consumption. Furthermore, both animal and human trials suggest a greater satiating effect of medium-chain triglycerides (MCT) compared with long-chain triglycerides (LCT). The aim of this review is to evaluate existing data describing the effects of MCT on EE and satiety and determine their potential efficacy as agents in the treatment of human obesity. Animal studies are summarized and human trials more systematically evaluated because the primary focus of this article is to examine the effects of MCT on human energy metabolism and satiety. Hormones including cholescytokinin, peptide YY, gastric inhibitory peptide, neurotensin and pancreatic polypeptide have been proposed to be involved in the mechanism by which MCT may induce satiety; however, the exact mechanisms have not been established. From the literature reviewed, we conclude that MCT increase energy expenditure, may result in faster satiety and facilitate weight control when included in the diet as a replacement for fats containing LCT.
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PMID:Physiological effects of medium-chain triglycerides: potential agents in the prevention of obesity. 1188 May 49

Neuropeptide Y (NPY) in the central nervous system is a major regulator of food consumption and energy homeostasis. It also regulates blood pressure, induces anxiolysis, enhances memory retention and affects circadian rhythms, as well as modulates hormone release. Five Y receptors are known that mediate the action of NPY and its two other family members, peptide YY and pancreatic polypeptide. Increased NPY signaling due to elevated NPY expression in the hypothalamus leads to the development of obesity and its related phenotypes, type 2 diabetes and cardiovascular disease. Dysregulation in NPY signaling also causes alterations in bone formation. The large number of Y receptors has made it difficult to delineate their individual contributions to these physiological processes. However, recent studies analyzing Y-receptor knockout models have started to unravel some of the individual functions of these Y receptors. Particularly, the use of conditional knockout models has made it possible to pinpoint a specific functional contribution to an individual Y receptor in a particular location. From these studies, the predominantly presynaptically expressed Y2 receptor in the arcuate nucleus of the hypothalamus has emerged as a prime candidate for mediating satiety as well as a candidate for regulating bone formation. (c) 2002 Prous Science. All rights reserved.
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PMID:Hypothalamic Y2 Receptors: Central Coordination of Energy Homeostasis and Bone Mass Regulation. 1267 89

Neuropeptides play an important role in the regulation of feeding behavior and obesity. The mechanisms for controlling food intake involve a complicated interplay between peripheral systems (including gustatory stimulation, gastrointestinal peptide secretion, and vagal afferent nerve responses) and central nervous system (CNS) neuropeptides and/or monoamines. These neuronal systems include neuropeptides (CRH, opioids, neuropeptide-Y (NPY) and peptide YY (PYY), vasopressin and oxytocin, CCK, and leptin) and monamines (serotonin, dopamine, norepinephrine). In addition to regulating eating behavior, a number of CNS neuropeptides participate in the regulation of neuroendocrine pathways. Thus, clinical studies have evaluated the possibility that CNS neuropeptide alterations may contribute to dysregulated secretion of the gonadal hormones, cortisol, thyroid hormones and growth hormone in the eating disorders. Most of the neuroendocrine and neuropeptide alterations apparent during symptomatic episodes of AN and BN tend to normalize after recovery. This observation suggests that most of the disturbances are consequences rather than causes of malnutrition, weight loss and/or altered meal patterns. Still, an understanding of these neuropeptide disturbances may shed light on why many people with AN or BN cannot easily "reverse" their illness and even after weight gain and normalized eating patterns, many individuals who have recovered from AN or BN have physiological, behavioral and psychological symptoms that persist for extended periods of time.
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PMID:A review of neuropeptide and neuroendocrine dysregulation in anorexia and bulimia nervosa. 1276 12

Obesity is a growing epidemic, causally associated with a number of serious medical conditions, including diabetes mellitus, coronary heart disease, and several cancers. The gut hormones ghrelin and peptide YY are secreted from the gut in response to changes to nutritional status. While food intake is stimulated by ghrelin, it is inhibited by peptide YY. The discovery, anatomy, and physiology of ghrelin and peptide YY are discussed, focusing on the adaptive changes in diseases such as obesity and anorexia nervosa. Ghrelin and PYY are important therapeutic targets in the quest to find an effective antiobesity treatment.
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PMID:Gut and mind. 1280 49

Neurons of the arcuate nucleus of the hypothalamus (ARH) appear to be sites of convergence of central and peripheral signals of energy stores, and profoundly modulate the activity of the melanocortin circuits, providing a strong rationale for pursuing these circuits as therapeutic targets for disorders of energy homeostasis. Recently, tremendous advances have been made in identifying genes and pathways important to regulating energy homeostasis, particularly the hormone leptin and its receptor. This hormone/receptor pair is expressed at high levels in the so-called satiety centers in the hypothalamus, and at lower levels elsewhere in the body. Recent studies in our lab and those of our collaborators have shown that leptin modulates different populations of hypothalamic cells in different ways, rapidly activating POMC neurons and inhibiting NPY/AgRP neurons. In this report, we outline an integrated model of leptin's action in the arcuate nucleus of the hypothalamus, derived from our electrophysiological studies of brain slice preparations taken from transgenic mice that have been bred to express a variety of fluorescent proteins in specific cell types. We also discuss the recently withdrawn obesity drug fenfluramine, which appears to act on POMC neurons via the serotonin 2C receptor. Nutrient-sensing serotonin neurons may project from the raphe nuclei in the brainstem to the hypothalamus; within the arcuate nucleus, serotonin signals are integrated with others such as leptin, ghrelin, and peptide YY(3-36) from the gut, to produce a coordinated response to nutrient state. Finally, we review the current inquiries into the ability of the hormone ghrelin to stimulate appetite by its action of NPY neurons and inhibition of POMC neurons.
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PMID:Electrophysiological actions of peripheral hormones on melanocortin neurons. 1285 14

A complex system has evolved to regulate food intake and to maintain energy homeostasis. A series of short-term hormonal and neural signals that derive from the gastrointestinal tract, such as cholecystokinin (CCK), pancreatic polypeptide (PP) and peptide YY-(3-36), recently discovered to regulate meal size. Others such as ghrelin initiate meals, and insulin and leptin, together with circulating nutrients, indicate long-term energy stores. All these signals act on central nervous system sites which converge on the hypothalamus, an area that contains a large number of peptide and other neurotransmitters that influence food intake with neuropeptide Y (NPY) being one of the most prominent ones. Five Y receptors are known which mediate the action of neuropeptide Y and its two other family members, peptide YY and pancreatic polypeptide. Elevated neuropeptide Y expression in the hypothalamus leads to the development of obesity and its related phenotypes, Type II diabetes and cardiovascular disease. The limited availability of specific pharmacological tools and the considerable number of Y receptors have made it difficult to delineate their individual contributions to the regulation of energy homeostasis. However, recent studies analysing transgenic and knockout neuropeptide Y and Y receptor mouse models have started to unravel some of the individual functions of these Y receptors potentially also helping to develop novel therapeutics for a variety of physiological disorders including obesity.
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PMID:Neuropeptide Y and energy homeostasis: insights from Y receptor knockout models. 1462 47

AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that acts as an intracellular energy sensor maintaining the energy balance within the cell. The finding that leptin and adiponectin activate AMPK to alter metabolic pathways in muscle and liver provides direct evidence for this role in peripheral tissues. The hypothalamus is a key regulator of food intake and energy balance, coordinating body adiposity and nutritional state in response to peripheral hormones, such as leptin, peptide YY-(3-36), and ghrelin. To date the hormonal regulation of AMPK in the hypothalamus, or its potential role in the control of food intake, have not been reported. Here we demonstrate that counter-regulatory hormones involved in appetite control regulate AMPK activity and that pharmacological activation of AMPK in the hypothalamus increases food intake. In vivo administration of leptin, which leads to a reduction in food intake, decreases hypothalamic AMPK activity. By contrast, injection of ghrelin in vivo, which increases food intake, stimulates AMPK activity in the hypothalamus. Consistent with the effect of ghrelin, injection of 5-amino-4-imidazole carboxamide riboside, a pharmacological activator of AMPK, into either the third cerebral ventricle or directly into the paraventricular nucleus of the hypothalamus significantly increased food intake. These results suggest that AMPK is regulated in the hypothalamus by hormones which regulate food intake. Furthermore, direct pharmacological activation of AMPK in the hypothalamus is sufficient to increase food intake. These findings demonstrate that AMPK plays a role in the regulation of feeding and identify AMPK as a novel target for anti-obesity drugs.
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PMID:AMP-activated protein kinase plays a role in the control of food intake. 1474 38

The gastrointestinal tract and the pancreas release hormones regulating satiety and body weight. Ghrelin stimulates appetite, and glucagon-like peptide-1, oxyntomodulin, peptide YY, cholecystokinin, and pancreatic polypeptide inhibit appetite. These gut hormones act to markedly alter food intake in humans and rodents. Obesity is the current major cause of premature death in the United Kingdom, killing almost 1000 people per week. Worldwide, its prevalence is accelerating. There is currently no effective answer to the pandemic of obesity, but replacement of the low levels of peptide YY observed in the obese may represent an effective antiobesity therapy.
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PMID:Minireview: Gut peptides regulating satiety. 1504 53

Obesity is a major health problem and as a result, it is reasonable to consider pharmacological approaches alongside approaches involving diet, physical activity and lifestyle change. The currently available drugs, sibutramine and orlistat, result in modest, clinically worthwhile weight loss, with demonstrable improvements in co-morbidity, but do not meet the often unrealistic expectations of patients or health care professionals managing obese patients. There is insufficient data on efficacy or safety of other agents to support their use. Many new pharmacological approaches are under investigation. These include gut hormones, such a peptide YY (3-36) and cholecystokinin that normally signal satiety, and centrally-acting agents such as serotonin agonists, the anticonvulsants topiramate and zonisamide, cannabinoid receptor antagonists and drugs that act on other peptide neurotransmitter systems such as NPY and the melanocortins. Given the multiple pathways that influence energy balance, it is likely that therapies targeting more than one control system may be required in the future to meet the expectations and needs of patients needing to lose weight for medical reasons.
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PMID:Clinical evaluation of anti-obesity drugs. 1505 16

Inactivating mutations of the pro-opiomelanocortin (POMC) gene in both mice and humans leads to hyperphagia and obesity. To further examine the mechanisms whereby POMC-deficiency leads to disordered energy homeostasis, we have generated mice lacking all POMC-derived peptides. Consistent with a previously reported model, Pomc(-/-) mice were obese and hyperphagic. They also showed reduced resting oxygen consumption associated with lowered serum levels of thyroxine. Hypothalami from Pomc(-/-) mice showed markedly increased expression of melanin-concentrating hormone mRNA in the lateral hypothalamus, but expression of neuropeptide Y mRNA in the arcuate nucleus was not altered. Provision of a 45% fat diet increased energy intake and body weight in both Pomc(-/-) and Pomc(+/-) mice. The effects of leptin on food intake and body weight were blunted in obese Pomc(-/-) mice whereas nonobese Pomc(-/-) mice were sensitive to leptin. Surprisingly, we found that Pomc(-/-) mice maintained their acute anorectic response to peptide-YY(3-36) (PYY(3-36)). However, 7 days of PYY(3-36) administration had no effect on cumulative food intake or body weight in wild-type or Pomc(-/-) mice. Thus, POMC peptides seem to be necessary for the normal response of energy balance to high-fat feeding, but not for the acute anorectic effect of PYY(3-36) or full effects of leptin on feeding. The finding that the loss of only one copy of the Pomc gene is sufficient to render mice susceptible to the effects of high fat feeding emphasizes the potential importance of this locus as a site for gene-environment interactions predisposing to obesity.
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PMID:Mice lacking pro-opiomelanocortin are sensitive to high-fat feeding but respond normally to the acute anorectic effects of peptide-YY(3-36). 1507 Jul 80


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