Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dietary modification is useful in both type 1 and type 2 diabetes. Glucose levels after a meal are largely determined by carbohydrate intake. Decreased intake of simple carbohydrates and increased fiber consumption lower postprandial glucose. Obesity has become epidemic in the United States and has dramatically increased the incidence of type 2 diabetes by augmenting insulin resistance. Dietary treatment of obesity has been frustrating. Success will require education in using foods with high fiber contents, low glycemic indexes, and low saturated fat levels. The use of natural foods must be supplemented by the use of semisynthetic foods with desirable properties. The educational efforts required are substantial and must be recognized by third-party reimbursement agencies. Operative procedures to decrease intake or reduce the absorption of food are being used with increasing frequency. Bariatric surgery is often successful in inducing a substantial loss of weight; however, this success must be balanced against the complications of surgery, which can be considerable. The pharmacologic approaches to treatment of obesity have focused primarily on anorexigenic agents. Several polypeptides that induce satiety are currently under study, including leptin and glucagon-like peptide-1 (GLP-1). Orlistat has been used to induce the malabsorption of fat to reduce caloric ingestion. Of the currently used oral hypoglycemics, metformin and the disaccharidase inhibitors have the best tendency to promote weight loss. There is active research on the uncoupling proteins that induce thermogenesis and promote the dissipation of calories. The beta-3 agonists act through the uncoupling proteins. The thiazolidinediones tend to promote weight gain through the PPAR gene locus. Agents that antagonize this effect could induce weight loss. The future will undoubtedly bring us drugs that are effective in causing weight loss. The advent of drugs to successfully combat obesity will substantially improve public health.
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PMID:Advances in diabetes for the millennium: nutritional therapy of type 2 diabetes. 1564 15

PPAR(alpha, beta/delta, gamma) are ligand-dependent nuclear receptors and regulate homeostasis, cell proliferation/differentiation and associate with hypolipidemia, atherosclerosis, diabetes, and obesity. Through heterodimerization with retinoid X receptors (RXRs), PPARs bind the same consensus response element, formed by a direct repeat of two AGGTCA hexamers separated by one base. Recently, many PPAR direct and indirect target genes have been reported. Here, we summarize the PPAR direct/indirect target genes, and their functions related to lipid metabolism, adipocyte differentiation.
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PMID:[PPARs target genes]. 1582 22

The effects of fatty acids and retinoic acid (carotene) on brown adipose tissue differentiation are mediated by activation of the transcription factors PPARgamma and PPARalpha in combination with RXR. There is good support for the idea that activated PPARgamma promotes adipogenesis also in brown adipose tissue. However, the issue is more complex concerning the full differentiation to the brown adipocyte phenotype, particularly the expression of the brown-fat-specific marker UCP1. The effect of norepinephrine on PPARgamma gene expression, at least in-vitro, is negative, PPARgamma-ablated brown adipose tissue can express UCP1, and PGC-1alpha coactivates other transcription factors (including PPARalpha); thus, the significance of PPARgamma for the physiological control of UCP1 gene expression is not settled. However, importantly, the effects of PPAR agonists demonstrate the existence of a pathway for brown adipose tissue recruitment that is not dependent on chronic adrenergic stimulation and may be active in recruitment conditions such as prenatal and prehibernation recruitment. The ability of chronic PPARgamma agonist treatment to promote the occurrence of brown-fat features in white adipose tissue-like depots implies a role in anti-obesity treatment, but this will only be effective if the extra thermogenic capacity is activated by adrenergic stimulation.
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PMID:PPARgamma in the control of brown adipocyte differentiation. 1594 96

Insulin resistance has a genetic background and its phenotypic expression is triggered by fat diet, lack of physical activity and obesity. It provokes a stress on B cells, tends to increase blood glucose levels, is intimately associated with the metabolic syndrome and represents a major cardiovascular risk factor. Insulin resistance may be favourably influenced by simple life-style changes. If necessary, drugs may be prescribed, such as metformin, the first choice antidiabetic oral agent in overweight individuals, or thiazolidinediones (glitazones), new insulin sensitizers with promising effects. New molecules are currently developed, especially PPAR alpha/gamma or pan-agonists. Targeting insulin resistance has several objectives: reducing hyperglycaemia in type 2 diabetic patients, protecting B cells in order to prevent type 2 diabetes in at risk individuals and limiting the progressive metabolic deterioration in diabetic patients, finally, and perhaps most importantly, ameliorating the global cardiovascular prognosis.
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PMID:[Insulin sensitizers]. 1603 2

Obese (fa/fa) Zucker rat is a spontaneous genetic obesity model and, by comparison with lean Zucker rat, exhibits hyperphagia, hyperinsulinemia, and hyperlipidemia. The aim of this study was to examine the physiological difference concerning adiponectin between obese (fa/fa) Zucker rats and control lean Zucker rats. We therefore measured plasma adiponectin level and analyzed adiponectin and adiponectin receptor 1 mRNA expression in retroperitoneal white adipose tissue (RT WAT), brown adipose tissue (BAT), liver, and soleus muscle. We also examined the tissue mRNA expression of peroxisome proliferator-activated receptor alpha (PPAR alpha), PPAR delta, and PPAR gamma, which regulate adiponectin expression sensitivity to a PPAR gamma agonist shown by brown adipocytes from obese (fa/fa) Zucker rats and lean Zucker rats, by measuring adiponectin release from these cells. Plasma adiponectin levels of obese (fa/fa) Zucker rats were significantly higher than those of lean Zucker rats. Adiponectin mRNA expression levels in RT WAT were lower in obese (fa/fa) Zucker rats than in lean Zucker rats, but those in BAT were higher. Adiponectin receptor 1 expression levels in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats were lower than in lean Zucker rats. The expression level of PPAR alpha, PPAR delta, and PPAR gamma in BAT was lower in obese (fa/fa) Zucker rats than in lean Zucker rats. Moreover, the PPAR gamma agonist increased adiponectin release only from the brown adipocytes isolated from lean Zucker rats. It is the conclusive difference between obese (fa/fa) Zucker rats and lean Zucker rats that plasma adiponectin levels of obese (fa/fa) Zucker rats are significantly higher than those of lean Zucker rats. Moreover, we clarified that mRNA expression level of adiponectin receptor 1 in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats is low despite high plasma adiponectin level, and low expression of PPARs in BAT leads to less sensibility of adiponectin release from brown adipocytes to a PPAR gamma agonist in obese (fa/fa) Zucker rats.
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PMID:Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin. 1609 47

Metabolism, in part, is regulated by the peroxisome proliferator-activated receptors (PPARs). The PPARs act as nutritional lipid sensors and three mammalian PPAR subtypes designated PPARalpha (NR1C1), PPARgamma (NR1C3) and PPARdelta (NR1C2) have been identified. This subgroup of nuclear hormone receptors binds DNA and controls gene expression at the nexus of pathways that regulate lipid and glucose homeostasis, energy storage and expenditure in an organ-specific manner. Recent evidence has demonstrated activation of PPARdelta in the major mass peripheral tissue (ie, adipose and skeletal muscle). It enhances glucose tolerance, insulin-stimulated glucose disposal, lipid catabolism, energy expenditure, cholesterol efflux and oxygen consumption. These effects positively influence the blood-lipid profile. Furthermore, PPARdelta activation produces a predominant type I/slow twitch/oxidative muscle fiber phenotype that leads to increased endurance, insulin sensitivity and resistance to obesity. PPARdelta has rapidly emerged as a potential target in the battle against dyslipidemia, insulin insensitivity, type II diabetes and obesity, with therapeutic efficacy in the treatment of cardiovascular disease risk factors. GW-501516 is currently undergoing phase II safety and efficacy trials in human volunteers for the treatment of dyslipidemia. The outcome of these clinical trials are eagerly awaited against a background of conflicting reports about cancer risks in genetically predisposed animal models. This review focuses on the potential pharmacological utility of selective PPARdelta agonists in the context of risk factors associated with metabolic and cardiovascular disease.
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PMID:Cardiovascular disease and PPARdelta: targeting the risk factors. 1618 88

Obesity is a growing threat to global health by virtue of its association with insulin resistance, glucose intolerance, hypertension, and dyslipidemia, collectively known as the metabolic syndrome or syndrome X. The nuclear receptors PPARalpha and PPARgamma are therapeutic targets for hypertriglyceridemia and insulin resistance, respectively, and drugs that modulate these receptors are currently in clinical use. More recent work on the less-described PPAR isotype PPARdelta has uncovered a dual benefit for both hypertriglyceridemia and insulin resistance, highlighting the broad potential of PPARdelta in the treatment of metabolic disease. PPARdelta enhances fatty acid catabolism and energy uncoupling in adipose tissue and muscle, and it suppresses macrophage-derived inflammation. Its combined activities in these and other tissues make it a multifaceted therapeutic target for the metabolic syndrome with the potential to control weight gain, enhance physical endurance, improve insulin sensitivity, and ameliorate atherosclerosis.
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PMID:PPAR delta: a dagger in the heart of the metabolic syndrome. 1651 91

Zucker fatty rats and ob/ob mice are both frequently used hyperlipidemic and insulin-resistant spontaneous genetic models of obesity. We used them to study the effect of PPAR agonists on the protein-expression level in liver and white adipose tissue. PPARalpha-agonist treatments of the rats resulted in that 27% of the quantified hepatic proteins were altered; implicating pronounced peroxisome proliferation and increase in capacity for beta-oxidation of fatty acids although no correction of plasma triglycerides were obtained. On treatment with PPARgamma agonists, adipose proteins were regulated to a much larger extent in the rats compared to mice, 18% and 2%, respectively.
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PMID:PPARalpha and PPARgamma regulation of liver and adipose proteins in obese and dyslipidemic rodents. 1688 6

A new approach, SiteGA, for the prediction of functional transcription factor binding sites has been developed. The approach is based on the detection of locally positioned dinucleotides by the genetic algorithm and discriminant analysis. The approach has been applied to recognize transcription factor binding sites involved in the regulation of immune responses and cell growth (AP-1, IRF1, ISGF3, NFkappaB, STAT1), obesity and lipid metabolism (HNF4, PPAR, SREBP), and the expression of steroidogenesis genes (SF-1). SiteGA is far superior in accuracy to the traditionally used method of position weight matrices. The approach was implemented in the web tool, SiteGA http://wwwmgs2. bionet.nsc.ru/mgs/programs/sitega.
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PMID:[Method SiteGA for the recognition of transcription factor binding sites]. 1690 40

Exercise training and regular physical activity increase oxidation of fat. Enhanced oxidation of fat is important for preventing lifestyle diseases such as hypertension and obesity. The aim of the present study in rats was to determine whether intake of dietary soya protein and exercise training have an additive effect on the activity and mRNA expression of enzymes involved in skeletal muscle fatty acid oxidation. Male Sprague-Dawley rats (n 32) were assigned randomly into four groups (eight rats per group) and then divided further into sedentary or exercise-trained groups fed either casein or soya protein diets. Rats in the exercise groups were trained for 2 weeks by swimming for 120 min/d, 6 d/week. Exercise training decreased hepatic triacylglycerol levels and retroperitoneal adipose tissue weight and increased skeletal muscle carnitine palmitoyltransferase 1 (CPT1) activity and mRNA expression of CPT1, beta-hydroxyacyl-CoA dehydrogenase (HAD), acyl-CoA oxidase, PPARgamma coactivator 1alpha (PGC1alpha) and PPARalpha. Soya protein significantly decreased hepatic triacylglycerol levels and epididymal adipose tissue weight and increased skeletal muscle CPT1 activity and CPT1, HAD, acyl-CoA oxidase, medium-chain acyl-CoA dehydrogenase, PGC1alpha and PPARalpha mRNA levels. Furthermore, skeletal muscle HAD activity was the highest in exercise-trained rats fed soya protein. We conclude that exercise training and soya protein intake have an important additive role on induction of PPAR pathways, leading to increased activity and mRNA expression of enzymes involved in fatty acid oxidation in skeletal muscle and reduced accumulation of body fat.
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PMID:Dietary soya protein intake and exercise training have an additive effect on skeletal muscle fatty acid oxidation enzyme activities and mRNA levels in rats. 1692 51


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