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)

The G-protein-coupled receptor GPR74 is a novel candidate gene for body weight regulation. In humans, it is predominantly expressed in brain, heart, and adipose tissue. We report a haplotype in the GPR74 gene, ATAG, with allele frequency ~4% in Scandinavian cohorts, which was associated with protection against obesity in two samples selected for obese and lean phenotypes (odds ratio for obesity 0.48 and 0.62; nominal P=.0014 and .014; n=1,013 and 1,423, respectively). In a population-based sample, it was associated with lower waist (P=.02) among 3,937 men and with obesity protection (odds ratio 0.36; P=.036) among those selected for obese or lean phenotypes. The ATAG haplotype was associated with increased adipocyte lipid mobilization (lipolysis) in vivo and in vitro. In human fat cells, GPR74 receptor stimulation and inhibition caused a significant and marked decrease and increase, respectively, of lipolysis, which could be linked to catecholamine stimulation of adipocytes through beta -adrenergic receptors. These findings suggest that a common haplotype in the GPR74 gene protects against obesity, which, at least in part, is caused by a relief of inhibition of lipid mobilization from adipose tissue. The latter involves a cross-talk between GPR74 and beta -adrenoceptor signaling to lipolysis in fat cells.
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PMID:A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis. 1750 29

Adipose tissue morphology and release of free fatty acids, as well as peptide hormones, are believed to contribute to obesity and related metabolic disorders. These adipose tissue phenotypes are influenced by adiposity, but there is also a strong hereditary impact. Polymorphisms in numerous adipose-expressed genes have been evaluated for association with adipocyte and clinical phenotypes. In our opinion, some results are convincing. Thus ADRB2 and GPR74 genes are associated with adipocyte lipolysis, GPR74 also with BMI; PPARG and SREBP1, which promote adipogenesis and lipid storage, are associated with T2D and possible adiposity; ADIPOQ and ARL15 are associated with circulating levels of adiponectin, ARL15 also with coronary heart disease. We anticipate that the use of complementary approaches such as expression profiling and RNAi screening, and studies of additional levels of gene regulation, that is, miRNA and epigenetics, will be important to unravel the genetics of adipose tissue function.
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PMID:Genetics of adipose tissue biology. 2103 22