Molecular mechanisms of insulin resistance and the role of the adipocyte. Export

@article{citeulike:787141, abstract = {Insulin resistance is a common feature of obesity and predisposes the affected individuals to a variety of diseases, including hypertension, dyslipidemias, cardiovascular problems and type 2 diabetes mellitus. However, the molecular mechanisms underlying abnormal insulin action and these other pathological states are not well understood. We have been focusing on cytokines, particularly TNFalpha and fatty acid binding proteins, as potential sites to study the molecular basis of these disorders. The role of TNFalpha in insulin resistance and other pathologies associated with obesity, have been examined in several experimental systems including obese mice with homozygous null mutations at the TNFalpha or TNF receptor loci. Analysis of these animals demonstrated that the genetic absence of TNF signaling in obesity: (i) significantly improves insulin receptor signaling capacity and consequently insulin sensitivity; (ii) prevents brown adipose tissue atrophy and beta3-adrenoreceptor deficiency and improves thermo-adaptive responses, (iii) decreases the elevated PAI-1 and TGFbeta production; and (iv) lowers hyperlipidemia and hyperleptinemia. Hence, abnormal TNFalpha action in adipocytes disturbs many aspects of metabolic homeostasis in obesity.}, address = {School of Public Health, Harvard University, Boston, Massachusetts 02115, USA. ghotamis@hsph.harvard.edu}, author = {Hotamisligil, G. S.}, citeulike-article-id = {787141}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/11126235}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=11126235}, issn = {0307-0565}, journal = {Int J Obes Relat Metab Disord}, keywords = {2, acid, adipocyte, adipose, biology, biosci353, cell, diabetes, disease, fatty, free, insulin, mechanisms, mellitus, molecular, pathogenesis, resistance, tissue, type}, month = {November}, posted-at = {2006-08-06 04:34:22}, priority = {2}, title = {Molecular mechanisms of insulin resistance and the role of the adipocyte.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/11126235}, volume = {24 Suppl 4}, year = {2000} }

TY - JOUR ID - citeulike:787141 L3 - citeulike-article-id:787141 N2 - Insulin resistance is a common feature of obesity and predisposes the affected individuals to a variety of diseases, including hypertension, dyslipidemias, cardiovascular problems and type 2 diabetes mellitus. However, the molecular mechanisms underlying abnormal insulin action and these other pathological states are not well understood. We have been focusing on cytokines, particularly TNFalpha and fatty acid binding proteins, as potential sites to study the molecular basis of these disorders. The role of TNFalpha in insulin resistance and other pathologies associated with obesity, have been examined in several experimental systems including obese mice with homozygous null mutations at the TNFalpha or TNF receptor loci. Analysis of these animals demonstrated that the genetic absence of TNF signaling in obesity: (i) significantly improves insulin receptor signaling capacity and consequently insulin sensitivity; (ii) prevents brown adipose tissue atrophy and beta3-adrenoreceptor deficiency and improves thermo-adaptive responses, (iii) decreases the elevated PAI-1 and TGFbeta production; and (iv) lowers hyperlipidemia and hyperleptinemia. Hence, abnormal TNFalpha action in adipocytes disturbs many aspects of metabolic homeostasis in obesity. JF - Int J Obes Relat Metab Disord SN - 0307-0565 AD - School of Public Health, Harvard University, Boston, Massachusetts 02115, USA. ghotamis@hsph.harvard.edu TI - Molecular mechanisms of insulin resistance and the role of the adipocyte. VL - 24 Suppl 4 KW - 2 KW - acid KW - adipocyte KW - adipose KW - biology KW - biosci353 KW - cell KW - diabetes KW - disease KW - fatty KW - free KW - insulin KW - mechanisms KW - mellitus KW - molecular KW - pathogenesis KW - resistance KW - tissue KW - type AU - Hotamisligil, GS PY - 2000/11// UR - http://view.ncbi.nlm.nih.gov/pubmed/11126235 ER -