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

We compared the current prevalence of increased BMI and type 2 diabetes in a representative group of Tongan subjects with measurements made in 1973, and we determined the distribution and possible interrelations with the UCP2 insertion/deletion (ins/del) polymorphism of these variables. We documented the BMI, glucose tolerance, and standard lipid variables in 1012 Tongan subjects (429 men and 583 women, ages 15 to 85 years) during 1998 and 2000 and compared the BMI findings with those of the 1973 survey. We also genotyped for the UCP2 ins/del polymorphism, assessed its association with obesity and type 2 diabetes, and compared its prevalence with those reported for other ethnic populations. The mean BMI +/- SD was greatly increased in both men (30.2 +/- 5.4 kg/m(2)) and women (33.8 +/- 6.2 kg/m(2)), representing increases since 1973 of 11.9% and 19.4%, respectively. The genotype frequencies were 97% for the del/del genotype and 3% for the ins/del genotype; we found no ins/ins homozygotes. This distribution is strikingly different from those reported for white, South Indian, Pima Native-American, and Asian populations (49 to 77% for del/del genotype). We conclude that there is a marked prevalence of obesity in Tonga, a prevalence that has increased since 1973. We also conclude that there is a unique, near-uniform distribution of the UCP2 45-bp ins/del polymorphism in Tongans. This may be the result of a founder effect and may be relevant to the prevalence of obesity and type 2 diabetes in Tonga.
 ...
PMID:A 45-bp insertion/deletion polymorphism of uncoupling protein 2 in relation to obesity in Tongans. 1269 79

It was reported that the common -866G/A polymorphism in the promoter of the human uncoupling protein-2 (UCP2) gene, which enhances its trascriptional activity, is associated with increased mRNA levels in human adipocytes and reduced risk of obesity. Studies in knockout mice and beta-cells indicate that UCP2 may play a role in beta-cell function. In this study, we addressed the question of whether the common -866G/A polymorphism in UCP2 gene contributes to the variation of insulin secretion in humans by genotyping 301 nondiabetic subjects who underwent an oral glucose tolerance test. Glucose-stimulated insulin secretion estimated by several indexes of beta-cell function was significantly lower in carriers of the -866A/A genotype compared with -866A/G or -866G/G according to the dosage of the A allele (P = 0.002-0.05). To investigate directly whether the UCP2 -866G/A polymorphism affects human islet function, pancreatic islets isolated from two -866G/G homozygous, seven -866G/A heterozygous, and one -866A/A homozygous nondiabetic donors were studied. Islets from -866A/A homozygous had lower insulin secretion in response to glucose stimulation as compared with -866G/G and -866G/A carriers. These results indicate that the common -866G/A polymorphism in the UCP2 gene may contribute to the biological variation of insulin secretion in humans.
 ...
PMID:A common polymorphism in the promoter of UCP2 contributes to the variation in insulin secretion in glucose-tolerant subjects. 1271 65

Energy exists as organic molecules and heat in living organisms. In adult mammals, body weight and fat content remain unchanged if energy intake is strictly equivalent to energy expenditure. In other words, regulation of body weight requires energy of foods to be entirely dissipated as heat. Imbalance between ingested energy and thermogenesis induces obesity or thinness. Alterations of food intake or energy expenditure represent the two causes of body weight disturbance. It is accepted that individuals differ in food efficiency i.e. ability to metabolize foods and store fat or totally burn nutrients. Mechanisms of food efficiency and futile cycles are presented. I started my research work analysing thermogenic mechanism in brown adipose tissue. Actually, in addition to white adipose tissue which is the major type of adipose tissue, mammals own another type of adipose tissue referred to as brown adipose tissue. This later tissue is an activatable thermogenic organ which oxidizes fatty acids and releases heat in blood stream. Brown fat is activated during exposure to the cold (in rodents), at birth, and during arousal in hibernators. My initial work helped to characterize a mitochondrial protein named uncoupling protein or UCP which is responsible for activation of fatty acid oxidation and heat production in brown adipocytes. Actually, in most cells, fifty per cent of oxidation energy is recovered as ATP in mitochondria through the process of coupling of respiration to ADP phosphorylation. In contrast to mitochondria of most tissues, brown adipocyte mitochondria can escape the obligatorily coupling of respiration and waste almost ninety per cent of respiration energy as thermogenesis. UCP characterization and its molecular cloning as well as antibodies obtention were used to better understand cellular thermogenesis. Brown adipocytes were identified in babies and adult patients with pheochromocytoma. More recently, research on the brown fat UCP helped us to identify UCP2, a UCP homolog present in most human and animal tissues. A family of UCPs exist in animals and plants. These UCPs may function as mitochondrial uncouplers. However, the ancient function of the UCPs may be rather associated to adaptation to oxygen and control of free radicals than to thermogenesis. Further studies of UCPs will improve the knowledge of mitochondrial metabolism and substrate oxidation. In other respects, analysis of molecular mechanisms controlling respiration uncoupling may contribute to new strategies of treatment of metabolic disorders such as obesity.
 ...
PMID:[To burn or to store]. 1273 25

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.
 ...
PMID:The role of uncoupling protein 2 in the development of type 2 diabetes. 1274 44

Recently, an association between obesity and the G-allele of the - 866 G/A polymorphism in the promoter region of uncoupling protein-2 gene (UCP2) was reported. Both allele frequencies and genotype distributions for this polymorphism differed between obese individuals and never-obese controls. We attempted to confirm this finding. Genotyping was performed by polymerase chain reaction with subsequent restriction fragment length polymorphism analysis (PCR-RFLP). We analysed transmission disequilibrium of the (wild type) G-allele for 200 extremely obese children and adolescents from 93 concordant sib pair families using the pedigree disequilibrium test. Additionally, using a one-sided asymptotic Pearson's chi 2-test, we tested whether the G-allele occurs more frequently in 277 extremely obese children and adolescents (including the 93 index patients of the concordant sib pairs) than in 188 never-obese controls. The one-sided asymptotic Cochran Armitage trend test was used to determine differences in genotype frequencies between extremely obese and healthy underweight individuals. The PDT analysis revealed no evidence for transmission disequilibrium in obesity. Allele and genotype frequencies did not differ between the extremely obese and never-obese subjects. In conclusion, we cannot confirm the results of ) in our young sample.
 ...
PMID:No evidence for involvement of the promoter polymorphism -866 G/A of the UCP2 gene in childhood-onset obesity in humans. 1274 56

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.
 ...
PMID:[Role of uncoupling proteins in obesity]. 1286 Dec 71

The onset of type 2 diabetes (T2DM) is preceded by obesity, insulin resistance, and impaired beta-cell function. Uncoupling protein-2 (UCP2) is a widely expressed inner mitochondrial membrane protein. Common polymorphisms of the UCP2 gene have been implicated in diabetes, in obesity, and with changes in UCP2 mRNA levels. We tested the hypothesis that common UCP2 variants influence T2DM susceptibility in four parallel studies of separate populations. We typed the -866 promoter (G/A) variant, a nonsynonymous (Ala55Val or A55V) single-nucleotide polymorphism in exon 4, and a 45-nt insertion in the 3'-untranslated (3'UTR) region. Study populations included a case-control population study, a family-based association study, and a metabolic study of individuals who had been characterized for insulin sensitivity and secretion. To evaluate UCP2 mRNA levels, we examined a fourth population of subjects, who had undergone subcutaneous fat biopsy. All three variants showed a trend to an association with T2DM (P = 0.05 to 0.07) in the population but not the family-based association study. The 3' insertion/deletion (3'UTR I/D) variant was associated with body mass index (BMI, P = 0.035) among nondiabetic family members. Haplotype combinations were significantly associated with BMI (P = 0.028), triglyceride levels (P = 0.026), and fasting insulin (P = 0.029); highest values for the three traits were observed in individuals with the heterozygous combination GVI/AVD. In the metabolic study, all three variants were associated with an index of beta-cell compensation for insulin sensitivity (disposition index), particularly in interaction with family membership (P < 0.000001). Individuals homozygous for the -866 A allele had decreased adipose mRNA levels relative to GG homozygous individuals (P = 0.009), but the 3'UTR I/D variant had no impact on mRNA levels. We confirm modest effects of UCP2 variants on BMI and T2DM and show significant effects on insulin secretion in interaction with family-specific factors. However, the associated allele and the effects on gene expression are opposite to those reported previously.
 ...
PMID:Uncoupling protein-2 polymorphisms in type 2 diabetes, obesity, and insulin secretion. 1291 97

Malonyl-CoA, generated by acetyl-CoA carboxylases ACC1 and ACC2, is a key metabolite in the control of fatty acid synthesis and oxidation in response to dietary changes. ACC2 is associated to the mitochondria, and Acc2-/- mice have a normal lifespan and higher fatty acid oxidation rate and accumulate less fat. Mutant mice fed high-fat/high-carbohydrate diets weighed less than their WT cohorts, accumulated less fat, and maintained normal levels of insulin and glucose, whereas the WT mice became type-2 diabetic with hyperglycemic and hyperinsulinemic status. Fatty acid oxidation rates in the soleus muscle and in hepatocytes of Acc2-/- mice were significantly higher than those of WT cohorts and were not affected by the addition of insulin. mRNA levels of uncoupling proteins (UCPs) were significantly higher in adipose, heart (UCP2), and muscle (UCP3) tissues of mutant mice compared with those of the WT. The increase in the UCP levels along with increased fatty acid oxidation may play an essential role in the regulation of energy expenditure. Lowering intracellular fatty acid accumulation in the mutant relative to that of the WT mice may thus impact glucose transport by higher GLUT4 activity and insulin sensitivity. These results suggest that ACC2 plays an essential role in controlling fatty acid oxidation and is a potential target in therapy against obesity and related diseases.
 ...
PMID:Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. 1292 Jan 82

To examine the peripheral and central roles of adiponectin in energy intake and expenditure, we investigated the effects of adiponectin on food intake, adiposity, sympathetic nerve activity (SNA), and mRNA expressions of uncoupling protein (UCP) in the brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in agouti yellow (A(y)/a) obese mice. Intraperitoneal administration of adiponectin (1.5 mg/kg for 7 days) attenuated body weight gain and reduced visceral adiposity in A(y)/a obese mice compared with PBS-treated controls. In addition, adiponectin treatment increased the expression of UCP1 mRNA in BAT, UCP2 mRNA in WAT, and UCP3 mRNA in skeletal muscle compared with PBS-treated A(y)/a controls. Acute peripheral administration of adiponectin (1.5 mg/kg, one injection) also increased SNA in the BAT accompanied by an increase in rectal temperature. Finally, these above responses as well as expression of c-Fos-like immunohistochemistry in the hypothalamus were not induced by central application of adiponectin (0-15 micro g/kg). Taken together, adiponectin effectively regulated visceral adiposity, SNA, and UCP mRNA expression peripherally, suggesting that this substance can be used as a therapeutic tool, administered peripherally, in the treatment of visceral obesity and related metabolic disorders.
 ...
PMID:Peripheral, but not central, administration of adiponectin reduces visceral adiposity and upregulates the expression of uncoupling protein in agouti yellow (Ay/a) obese mice. 1294 65

To elucidate the role of hormone-sensitive lipase (HSL) in diet-induced obesity, HSL-deficient (HSL-/-) and wild-type mice were fed normal chow or high-fat diets. HSL-/- mice were resistant to diet-induced obesity showing higher core body temperatures. Weight and triacylglycerol contents were decreased in white adipose tissue (WAT) but increased in both brown adipose tissue (BAT) and liver of HSL-/- mice. Serum insulin levels in the fed state and tumor necrosis factor-alpha mRNA levels in adipose tissues were higher, whereas serum levels of adipocyte complement-related protein of 30 kDa (ACRP30)/adiponectin and leptin, as well as mRNA levels of ACRP30/adiponectin, leptin, resistin, and adipsin in WAT, were lower in HSL-/- mice than in controls. Expression of transcription factors associated with adipogenesis (peroxisome proliferator-activated receptor-gamma, CAAT/enhancer-binding protein-alpha) and lipogenesis (carbohydrate response element-binding protein, adipocyte determination- and differentiation-dependent factor-1/sterol regulatory element-binding protein-1c), as well as of adipose differentiation markers (adipocyte lipid-binding protein, perilipin, lipoprotein lipase), lipogenic enzymes (glycerol-3-phosphate acyltransferase, acyl-CoA:diacylglycerol acyltransferase-1 and -2, fatty acid synthase, ATP citrate lyase) and insulin signaling proteins (insulin receptor, insulin receptor substrate-1, GLUT4), was suppressed in WAT but not in BAT of HSL-/- mice. In contrast, expression of genes associated with cholesterol metabolism (sterol-regulatory element-binding protein-2, 3-hydroxy-3-methylglutaryl-CoA reductase, acyl-CoA:cholesterol acyltransferase-1) and thermogenesis (uncoupling protein-2) was upregulated in both WAT and BAT of HSL-/- mice. Our results suggest that impaired lipolysis in HSL deficiency affects lipid metabolism through alterations of adipose differentiation and adipose-derived hormone levels.
 ...
PMID:Resistance to high-fat diet-induced obesity and altered expression of adipose-specific genes in HSL-deficient mice. 1295 98


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>