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

The central melanocortin system is perhaps the best-characterized neuronal pathway involved in the regulation of energy homeostasis. This collection of circuits is unique in having the capability of sensing signals from a staggering array of hormones, nutrients and afferent neural inputs. It is likely to be involved in integrating long-term adipostatic signals from leptin and insulin, primarily received by the hypothalamus, with acute signals regulating hunger and satiety, primarily received by the brainstem. The system is also unique from a regulatory point of view in that it is composed of fibers expressing both agonists and antagonists of melanocortin receptors. Given that the central melanocortin system is an active target for development of drugs for the treatment of obesity, diabetes and cachexia, it is important to understand the system in its full complexity, including the likelihood that the system also regulates the cardiovascular and reproductive systems.
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PMID:Anatomy and regulation of the central melanocortin system. 1585 65

In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. NPs have recently been found to exert potent lipolytic effects (ie, activating the breakdown of stored triacylglycerols) in isolated human fat cells and to promote lipid mobilization in vivo. Atrial natriuretic peptide increases the intracellular 3', 5'-cyclic guanosine monophosphate (cGMP) concentration which activates cGMP-dependent protein kinase leading to perilipin and hormone-sensitive lipase phosphorylation and lipolysis. NPs promote lipid mobilization when administered intravenously. NPs are also responsible for the residual lipid-mobilizing action observed under oral beta-blockade in subjects performing physical exercise. NPs are therefore novel factors which may open promising research pathways to explain the control of lipid mobilization in physiological and pathological conditions. The metabolic impact of altered production and circulation of NPs remains to be established. The potential influence of NPs on the development of lipid disorders, obesity-related cardiovascular events, and cardiac cachexia will be discussed in this review.
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PMID:An unsuspected metabolic role for atrial natriuretic peptides: the control of lipolysis, lipid mobilization, and systemic nonesterified fatty acids levels in humans. 1612 23

Several recent clinical trials using single modalities to correct the conventional cardiovascular risk factors in patients with chronic kidney disease (CKD) or to improve dialysis dose and techniques in maintenance dialysis patients have failed despite the high rate of cardiovascular mortality in these individuals. Protein-energy malnutrition and inflammation, two relatively common and concurrent conditions in CKD patients, have been implicated as the main cause of poor short-term survival in this population. The "malnutrition-inflammation-cachexia syndrome" (MICS) appears to be the main cause of worsening atherosclerotic cardiovascular disease in the CKD population. The MICS is associated with low serum cholesterol and homocysteine levels and leads to "cachexia in slow motion." Hence a reverse epidemiology of cardiovascular risk factors is observed in dialysis patients with a paradoxical association of obesity, hypercholesterolemia, and hyperhomocysteinemia with better survival. Correction of MICS can potentially ameliorate the cardiovascular epidemic in CKD patients. Because MICS is multifactorial, its correction will require an integral approach rather than a single intervention. The ongoing obsession with conventional cardiovascular risk factors largely reflecting overnutrition in a population that suffers from the short-term consequences of undernutrition and excessive inflammation may well be fruitless. Clinical trials focusing on the causes and consequences of MICS and its modulation using nutritional interventions may be the key to improving survival in these individuals.
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PMID:Recent advances in understanding the malnutrition-inflammation-cachexia syndrome in chronic kidney disease patients: What is next? 1619 Nov 72

Ghrelin is a 28 aminoacids peptide secreted from the stomach that stimulates the release of growth hormone (GH) from the anterior pituitary cells and is the strongest orexigenic hormone discovered so far. Ghrelin seems to be involved in the pathogenesis of obesity, anorexia nervosa and cachexia. Furthermore, low levels of ghrelin are negatively correlated with the degree of insulin resistance, blood pressure and the prevalence of type 2 diabetes. The role of ghrelin in the energy homeostasis and carbohydrate metabolism is discussed.
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PMID:[Ghrelin--role in energy homeostasis and glucose metabolism]. 1623 72

Since it was first realized that biological energy transduction involves oxygen and ATP, opinions about the amount of ATP made per oxygen consumed have continually evolved. The coupling efficiency is crucial because it constrains mechanistic models of the electron-transport chain and ATP synthase, and underpins the physiology and ecology of how organisms prosper in a thermodynamically hostile environment. Mechanistically, we have a good model of proton pumping by complex III of the electron-transport chain and a reasonable understanding of complex IV and the ATP synthase, but remain ignorant about complex I. Energy transduction is plastic: coupling efficiency can vary. Whether this occurs physiologically by molecular slipping in the proton pumps remains controversial. However, the membrane clearly leaks protons, decreasing the energy funnelled into ATP synthesis. Up to 20% of the basal metabolic rate may be used to drive this basal leak. In addition, UCP1 (uncoupling protein 1) is used in specialized tissues to uncouple oxidative phosphorylation, causing adaptive thermogenesis. Other UCPs can also uncouple, but are tightly regulated; they may function to decrease coupling efficiency and so attenuate mitochondrial radical production. UCPs may also integrate inputs from different fuels in pancreatic beta-cells and modulate insulin secretion. They are exciting potential targets for treatment of obesity, cachexia, aging and diabetes.
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PMID:The efficiency and plasticity of mitochondrial energy transduction. 1624 6

The melanocortin-4 (MC4) receptor is a potential therapeutic target for obesity and cachexia, for which nonpeptide agonists and antagonists are being developed, respectively. The aim of this study was to identify molecular interactions between the MC4 receptor and nonpeptide ligands, and to compare the mechanism of binding between agonist and antagonist ligands. Nonpeptide ligand interaction was affected by mutations that reduce peptide ligand binding (D122A, D126A, S190A, M200A, F261A, and F284A), confirming overlapping binding determinants for peptide and nonpeptide ligands. The common halogenated phenyl group of nonpeptide ligands was a determinant of F261A and F284A mutations' affinity-reducing effect, implying this group interacts with the aromatic side chains of these residues. All affected compounds contain this group, the mutations reduced binding of 2,4-dichloro-substituted compounds more than 4-chloro-substituted-compounds, and F284A mutation eliminated the affinity-enhancing effect of 2-chloro-substitution. F261A and F284A mutations reduced the affinity of antagonists more than agonists, suggesting that the stronger ligand interaction with these residues, the lower the ligand efficacy. Supporting this hypothesis, F261A mutation increased the efficacy of nonpeptide antagonist and partial agonist ligands. D122A and D126A mutations reduced nonpeptide ligand interaction. Removing the ligands' derivatized amide group eliminated the effect of the mutations. Interaction of agonists, which bear a common amine within this group, was strongly reduced by D126A mutation (550-3300-fold), suggesting an electrostatic interaction between the amine and the acidic group of D126. These postulated interactions with aromatic and acidic regions of the MC4 receptor are consistent with a molecular model of the receptor. Furthermore, the strength of interaction with the aromatic pocket, and potentially the acidic pocket, controls the signaling efficacy of the ligand.
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PMID:Molecular interactions of nonpeptide agonists and antagonists with the melanocortin-4 receptor. 1626 50

Weight regulation is a complex system necessary for maintaining health. Obesity and cachexia are consequences of dysregulation and cause significant physical morbidity and mortality. In the developed world, obesity is a growing epidemic. A greater understanding of the neuroanatomy of weight regulation has been gained through advances in imaging and neural mapping techniques. The neural connections between key hypothalamic and other central nuclei have been elucidated. Advances in molecular biology have led to the identification and cloning of important peripheral and central weight regulating peptides. Weight gain as a consequence of antipsychotic use is increasingly being recognized as a serious clinical issue. The weight regulation system provides a framework upon which antipsychotics exert their weight-inducing effects. Some studies have sought, with inconsistent results, to establish associations between antipsychotic use and levels of weight regulating mediators. The receptor pharmacology of antipsychotics known to increase weight can be studied with a view to establishing genetic variants contributing to the risk. To date, the 5-HT(2C) receptor 759C/T polymorphism shows most promise. Further studies are required to replicate previous findings and establish new associations.
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PMID:An overview of the central control of weight regulation and the effect of antipsychotic medication. 1628 Mar 36

Regulation of food intake and body weight depends on direct and feedback signals from adipose tissue, alimentary canal and pancreas to the hypothalamus nuclei, where hunger and satiety centers are. During the last decade a few signaling molecules of peptide origin were discovered, which play an important role in the regulation of energy intake and energy expenditure as well as in obesity. So, adipocytes synthesize and express leptin, the product of Ob gene, a regulator of long-term food intake, in amounts proportional to the fat amount, while alimentary canal hormones are regulators of short-term food intake (from meal to meal). Some peptides decrease food intake as they promote satiety (anorexigenic signals), other peptides, contrary, increase food intake as they induce appetite (orexigenic signals). Disturbed equilibrium between the anorexigenic and orexigenic factors manifests as food intake disorders, increase in body weight and obesity or decrease in body weight, i.e. cachexia.
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PMID:[Peptides regulating food intake and body weight]. 1640 55

In the population of pregnant women in Serbia and Montenegro, hemorrhoids are present in 85% of the cases during the second and third pregnancy. Urged by the complications of non-treated hemorrhoids, we carried out a routine diagnostic procedure to examine hemorrhoids during pregnancy, i.e. a differential diagnosis with other possible complications was performed. Fifty patients, aged between 36 and 38, were examined by anoscope and rectoscope during the second trimester. Rectal carcinoma was found in three cases, which is a disturbing number. The patient with the most serious clinical picture was subjected to urgent artificial fetal lung maturation and surgical delivery. One of the patients had clinical cachexia, and in view of the fact that the magnetic resonance imaging during pregnancy showed infiltration and that the patient was 38 years old, with the patient's consent, surgery was performed together with hysterectomy and salpingo-oophorectomy and immediate removal of the rectum and anus. In the other two cases, the delivery ended vaginally between the 35th and 38th week of gestation, after which the patients were moved to the surgery ward. Besides a positive family history for digestive tract carcinoma (95%), smoking and increased body mass index, there were no significant parameters distinguishing these three patients from others with hemorrhoids. Interesting data were obtained from the fact that there was no increase in body mass during pregnancy which patients correlated with their already present obesity. Moreover, pain was correlated with the fact that the patients did not follow a healthy dietary regime. In all 50 patients, the following procedures were performed: anoscope, rectoscope and digestive tract tumor markers. Observing the results of the biopsies, we found rectal carcinoma Stage C according to Dukes staging (tumor included serosa) in one case. In the other two cases, Stage B1 carcinomas were found (which included all layers except serosa). Magnetic resonance imaging was performed and confirmed progression of the disease. The delivery ended per vias naturalis in two cases in view of the fact that it was the third pregnancy for both patients. Surgery was performed 40 days after delivery. Postoperative recovery was unremarkable in all described cases.
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PMID:The significance of detailed examination of hemorrhoids during pregnancy. 1643 60

The melanocortins, a family of peptides produced from the post-translational processing of pro-opiomelanocortin (POMC), regulate ingestive behavior and energy expenditure. Loss of function mutations of genes encoding POMC, or of either of two melanocortin receptors expressed in the central nervous system (MC3R, MC4R), are associated with obesity. The analyses of MC4R knockout mice indicate that activation of this receptor is involved in the regulation of appetite, the adaptive metabolic response to excess caloric consumption, and negative energy balance associated with cachexia induced by cytokines. In contrast, MC3R knockout mice exhibit a normal, or even exaggerated, response to signals that induce a state of negative energy balance. However, loss of the MC3R also results in an increase in adiposity. This article discusses the regulation of energy balance by the melanocortins. Published and newly presented data from studies analyzing of energy balance of MC3R and MC4R knockout mice indicate that increased adiposity observed in both models involves an imbalance in fat intake and oxidation.
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PMID:The melanocortin system and energy balance. 1643 23


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