Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome

摘要: Insulin resistance, obesity, diabetes, dyslipidemia and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflammatory cytokines have been suggested to contribute development these disorders, molecular mechanism this syndrome poorly understood. In study, we show expression suppressor cytokine signaling SOCS-1 SOCS-3 increased livers obese insulin-resistant animals, adenoviral-mediated overexpression or causes insulin resistance through down-regulation tyrosine phosphorylation receptor substrate (IRS) proteins. Moreover, also cause prominent up-regulation key regulator acid synthesis liver, sterol regulatory element binding protein (SREBP)-1. Conversely, inhibition diabetic db/db mice by antisense treatment modestly improves sensitivity, but completely normalizes SREBP-1. The latter leads dramatic amelioration hepatic steatosis hypertriglyceridemia. Promoter activity analysis reveals with being more potent enhances SREBP-1c expression, while it inhibited STAT3. This STAT3-mediated antagonized co-expression SOCS display decreased STAT3 normalized These data suggest subjects persistent inflammatory states, such as elevated circulating tumor necrosis factor-alpha, may down-regulated proteins, leading liver. Thus, proteins play an important role pathogenesis concordantly modulating signaling.