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)

Uncoupling proteins (UCP) are carriers expressed in the mitochondrial inner membrane that uncouple oxygen consumption by the respiratory chain from ATP synthesis. UCP2 is a member of the multigenic UCP family that is expressed in a wide range of tissues and organs. Possible functions of UCP2 include control of ATP synthesis, regulation of fatty acid metabolism and control of reactive oxygen species production. UCP2 expression in tissues involved in lipid and energy metabolism and mapping of the gene to a region linked to obesity and hyperinsulinemia prompted studies on the involvement of UCP2 in metabolic disorders, and especially in type 2 diabetes. In human adipose tissue and skeletal muscle, UCP2 expression is increased during fasting. The carrier was shown to be under the control of fatty acids and thyroid hormones in vivo. An upregulation has been observed in the liver during high-fat feeding and obesity. However, data in UCP2 gene knockout mice do not support a role for UCP2 in steatohepatitis. The most compelling metabolic role of UCP2 comes from studies in pancreatic beta cells. Overexpression in isolated pancreatic islets results in decreased ATP content and blunted glucose-stimulated insulin secretion. UCP2-deficient mice show an increased ATP level and an enhanced insulin secretion. Lack of UCP2 dramatically improves insulin secretion and decreases hyperglycemia in leptin-deficient mice. The role of UCP2 in the control of insulin secretion constitutes, to date, the most pertinent path to investigate in a therapeutic perspective.
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PMID:The role of uncoupling protein 2 in the development of type 2 diabetes. 1274 44

The metabolic syndrome is a highly prevalent clinical entity. The recent Adult Treatment Panel (ATP III) guidelines have called specific attention to the importance of targeting the cardiovascular risk factors of the metabolic syndrome as a method of risk reduction therapy. The main factors characteristic of this syndrome are abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance (with or without glucose intolerance), prothrombotic and proinflammatory states. An insulin resistance following nuclear peroxisome proliferator activated receptors (PPAR) deactivation (mainly obesity-related) is the key phase of metabolic syndrome initiation. Afterwards, there are 2 principal pathways of metabolic syndrome development: 1) with preserved pancreatic beta cells function and insulin hypersecretion which can compensate for insulin resistance. This pathway leads mainly to the macrovascular complications of metabolic syndrome; 2) with massive damage of pancreatic beta cells leading to progressively decrease of insulin secretion and to hyperglycemia (e.g. overt type 2 diabetes). This pathway leads to both microvascular and macrovascular complications. We suggest that a PPAR-based appraisal of metabolic syndrome and type 2 diabetes may improve our understanding of these diseases and set a basis for a comprehensive approach in their treatment.
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PMID:Metabolic syndrome and type 2 diabetes mellitus: focus on peroxisome proliferator activated receptors (PPAR). 1283 41

The discovery of a protein of the internal mitochondrial membrane of the brown adipocytes, the UCP1, marked an important advance in the understanding of the thermogenic process, as well as of the working of the brown adipose tissue. This protein is only of importance in the newly born and small animals, however the later discovery of proteins that were analogues of UCP1 (UCP2, widely distributed, and UCP3, mainly present in the muscle) with a similar functioning and also present in human tissue, created new perspectives and scientific goals. These proteins uncouple the respiratory chain of the oxidative phosphorylation, thus dissipating energy in the form of heat without producing ATP, by means of a mechanism that is still the subject of debate. From the studies of regulation that have been made, it emerges that their activity is modified when facing different physiological and nutritional stimuli, with greater activity observed in situations where an increase of energy expenditure is required. The studies carried on humans seem to corroborate the results obtained in experiments on animals, and action can thus be proposed on the activity, or the quantity, of these proteins in humans, as a means for fighting overweightedness and obesity. However, there is still an evident need to complete and improve the existing information on the importance of these proton transporting proteins in humans.
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PMID:[Role of uncoupling proteins in obesity]. 1286 Dec 71

The recent focus on emerging cardiovascular risk factors, such as C-reactive protein, homocysteine, and small, dense low-density lipoprotein (LDL), may give the false impression that the current approach to the assessment of cardiovascular disease risk fails to identify a large section of the high-risk population. On the contrary, the new guidelines of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) propose classifying an enormous number of individuals, including people with any form of atherosclerotic disease, diabetes, and a combination of major risk factors, into the category of high risk (>20% likelihood of a major coronary event or stroke in 10 years). Considering the widespread prevalence of the metabolic syndrome-a high-risk condition characterized by mild hypertension, mild dyslipidemia, hyperglycemia, and visceral obesity-we may be faced with the challenge of implementing aggressive risk reduction therapies in as much as 30% of the adult US population. From the point of view of risk assessment, a practical approach is to follow the NCEP guidelines (ie, place patients with diabetes and those with atherosclerotic complications in the highest risk category), apply the Framingham calculation to determine risk in people with common risk factors, and initiate early intervention in people who have familial hypercholesterolemia (LDL cholesterol >200 mg/dL) or a family history of early cardiovascular disease. The emerging risk factors may be useful for further stratifying risk in individuals with intermediate risk and the presence of risk factors not included in the Framingham calculation.
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PMID:A practical approach to risk assessment to prevent coronary artery disease and its complications. 1286 51

The metabolic syndrome may be a common phenotype increasing risk for type 2 diabetes and cardiovascular disease. We assessed the prevalence and characteristics of the metabolic syndrome among population-based samples of 3,224 white subjects attending Framingham Offspring Study (FOS) exam 5 (1991-1995) and 1,081 non-Hispanic white and 1,656 Mexican-American subjects attending the San Antonio Heart Study (SAHS) phase II follow-up exam (1992-1996). Subjects were approximately 50% women, aged 30-79 years, without diabetes, and classified with the metabolic syndrome according to criteria for obesity, dyslipidemia, hyperglycemia, and hypertension proposed by the Third Report of the National Cholesterol Education Program's Adult Treatment Panel (ATP III) or the World Health Organization (WHO). We used regression models to estimate rates across ethnic groups and to assess the association of the metabolic syndrome with insulin resistance and predicted 10-year coronary heart disease (CHD) risk. Among FOS white subjects, the age- and sex-adjusted prevalence of the metabolic syndrome was 24% by both ATP III and WHO criteria; among SAHS non-Hispanic white subjects, 23 and 21%, respectively; and among SAHS Mexican-American subjects, 31 and 30%. Rates were highest among Mexican-American women (ATP III, 33%) and lowest among white women (21%). Subjects with the metabolic syndrome by ATP III criteria had higher age-, sex-, and ethnicity-adjusted levels of fasting insulin (11.3 micro U/ml), homeostasis model assessment of insulin resistance (2.7), and predicted CHD risk (11.8%) than those without the syndrome (5.9 micro U/ml, 1.3, and 6.4%, respectively; all P = 0.0001); differences were similar using WHO criteria. We conclude that the metabolic syndrome typically affects 20-30% of middle-aged adults in the U.S. By any criteria, subjects with the metabolic syndrome are more insulin resistant and at increased predicted risk for CHD versus those without the metabolic syndrome.
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PMID:Prevalence and characteristics of the metabolic syndrome in the San Antonio Heart and Framingham Offspring Studies. 1288 36

The thermogenic activity of brown adipose tissue (BAT), important for adaptive thermogenesis and energy expenditure, is mediated by the mitochondrial uncoupling protein1 (Ucp1) that uncouples ATP generation and dissipates the energy as heat. We show here that Cidea, a protein of unknown function sharing sequence similarity with the N-terminal region of DNA fragmentation factors Dffb and Dffa, is expressed at high levels in BAT. Cidea-null mice had higher metabolic rate, lipolysis in BAT and core body temperature when subjected to cold treatment. Notably, Cidea-null mice are lean and resistant to diet-induced obesity and diabetes. Furthermore, we provide evidence that the role of Cidea in regulating thermogenesis, lipolysis and obesity may be mediated in part through its direct suppression of Ucp1 activity. Our data thus indicate a role for Cidea in regulating energy balance and adiposity.
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PMID:Cidea-deficient mice have lean phenotype and are resistant to obesity. 1291 Feb 69

Obesity has reached epidemic proportions and has become one of the major health problems in developed countries. Current theories consider obesity a result of overeating and sedentary life style and most efforts to treat or prevent weight gain concentrate on exercise and food intake. This approach does not improve the situation as may be seen from the steep increase in the prevalence of obesity. This encouraged us to reanalyse existing information and look for biochemical basis of obesity. Our approach was to ignore current theories and concentrate on experimental data which are described in scientific journals and are available from several databases. We developed and applied a Knowledge Discovery in Databases procedure to analyse metabolic data. We began with the contradictory information: in obesity, more calories are consumed than used up, suggesting that obese people should have excess energy. On the other side, obese people experience fatigue and decreased physical endurance that indicates diminished energy supply in the body. The result of our work is a chain of metabolic events leading to obesity. The crucial event is the inhibition of the TCA cycle at the step of aconitase. It disturbs energy metabolism and results in ATP deficiency with simultaneous fat accumulation. Further steps in obesity development are the consequences of diminished energy supply: inhibition of beta-oxidation, leptin resistance, increase in appetite and food intake and a decrease in physical activity. Thus, our theory shows that obesity does not have to be caused by overeating and sedentary life-style but may be the result of the "obese" change in metabolism which is forcing people to overeat and save energy to sustain metabolic functions of cells. This "obese" change is caused by environmental factors that activate chronic low-grade inflammatory process in the body linking obesity with the environment of developed countries.
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PMID:Decreased energy levels can cause and sustain obesity. 1455 57

The metabolic syndrome is strongly related to visceral obesity and associated with a high risk of cardiovascular morbidity and mortality. Since the original description of Reaven in 1988, several working definitions have been proposed, especially by the World Health Organisation in 1998-99, the National Cholesterol Education Program (NCEP-ATP III) Expert Panel in the United States in 2001 and the European Group for the Study of Insulin Resistance (EGIR) in 2002. The present paper attempts at comparing these various definitions and at reporting epidemiological data both in North America and in Europe, especially in Belgium. The prevalence is generally higher in men than in women and strongly increases with age. Overall, one may estimate that around 20% of adults have a metabolic syndrome, which should therefore be considered as an important public health problem.
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PMID:[Metabolic syndrome: definitions and epidemiological data]. 1457 11

Relationships between insulin action and oxidative capacity in skeletal muscle have been suggested in humans, particularly in insulin-resistance-related metabolic disorders, such as obesity and diabetes. The regulatory action of insulin on fuel metabolism in insulin-sensitive tissues such as skeletal muscle is well documented, but the effect of insulin on muscle mitochondrial functions and oxidative capacity have yet to be defined in humans. In a recent article, Stump et al. investigated the stimulatory action of insulin on mitochondrial activities in key cellular events, such as ATP production, enzyme activity, mitochondrial protein synthesis, and mRNA expression of transcripts encoding mitochondrial proteins. To analyze the impact of insulin resistance on mitochondria, Stump et al. conducted their study in subjects with type 2 diabetes mellitus and in non-diabetic matched controls. Their results reveal that as well as being the predominant postprandial anabolic hormone for substrate utilization, insulin is also a major regulating factor of mitochondrial oxidative phosphorylation in human skeletal muscle.
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PMID:Insulin regulation of mitochondrial proteins and oxidative phosphorylation in human muscle. 1458 Jul 54

The purpose of this cross-sectional analysis is to examine modifiable CVD risk factors in relation to menopausal status, age, and length of residence in the U.S. of midlife women from the former Soviet Union. The analysis includes baseline data for 193 women, aged 40-70, who lived in the U.S. fewer than 8 years and were enrolled in an ongoing four-year study of post-immigration health and behavior change. Data collection was conducted in women's homes or other community locations. The presence of seven health risk indicators (obesity, dyslipidemia, high blood pressure, diabetes mellitus, sedentary lifestyle, smoking, and excessive alcohol use) was assessed. In addition, Framingham 10 year risk scores for heart disease, and the presence of metabolic syndrome, were calculated using recent National Cholesterol Education Program (ATP-III) guidelines. Consistent with the age distribution, 60% of the women were postmenopausal. Four risk indicators (obesity, dyslipidemia, high blood pressure, and sedentary lifestyle) were identified as significant areas of concern. Although the Framingham risk scores did not seem excessively high, almost 25% of the women had metabolic syndrome. Older and postmenopausal women had significantly higher scores on all risk estimates. When age and menopausal status were held constant, menopausal status remained an independent contributor for the number of CVD risk indicators. Issues specific to this group of women because of their pre- and post-migration lifestyles are discussed in relation to their CVD risk status.
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PMID:Cardiovascular disease risk factors and menopausal status in midlife women from the former Soviet Union. 1466 3


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