Indeed, in 267 HDAC inhibitor treatment-naïve Asian patients with CHB under entecavir treatment, steatosis has recently been reported to represent an
independent predictor of viral response, which, if confirmed by independent studies, would advise for a specific antiviral strategy in CHB patients with steatosis. Despite the limitations related to the cross-sectional design and the limited number of subjects considered with coexistent genetic and acquired risk factors for steatosis, strenghts of our study consist in the possibility to analyze one of the largest series of well-characterized biopsied CHB patients of Western countries with systematic assessment of liver steatosis and fibrosis as well as to evaluate, for the first time, the effect of the I148M PNPLA3 polymorphism on steatosis in CHB. In conclusion, the PNPLA3 I148M polymorphism is an independent predictor of steatosis and, especially, of severe steatosis in patients with CHB. The study also suggests that steatosis is highly
prevalent in Italian CHB patients with indications for liver biopsy and is related to genetic and metabolic, but not to viral, factors. “
“Obesity is associated with chronic inflammation and contributes to the development of insulin resistance and nonalcoholic fatty liver disease. The suppressor of cytokine signaling-3 (SOCS3) protein is increased in inflammation and is thought to contribute to the pathogenesis of insulin resistance by inhibiting insulin and leptin signaling. Therefore, we studied the metabolic effects of liver-specific SOCS3 deletion in vivo. We fed wild-type (WT) and liver-specific SOCS3 knockout (SOCS3 LKO) Trametinib order mice either a control diet or a high-fat diet (HFD) for 6 weeks and examined their metabolic phenotype.
We isolated hepatocytes from WT and SOCS3 LKO mice and examined the effects of tumor necrosis factor α and insulin on Akt phosphorylation and fatty acid metabolism and lipogenic gene expression. Branched chain aminotransferase Hepatocytes from control-fed SOCS3 LKO mice were protected from developing tumor necrosis factor α–induced insulin resistance but also had increased lipogenesis and expression of sterol response element–binding protein-1c target genes. Lean SOCS3 LKO mice fed a control diet had enhanced hepatic insulin sensitivity; however, when fed an HFD, SOCS3 LKO mice had increased liver fat, inflammation, and whole-body insulin resistance. SOCS3 LKO mice fed an HFD also had elevated hypothalamic SOCS3 and fatty acid synthase expression and developed greater obesity due to increased food intake and reduced energy expenditure. Conclusion: Deletion of SOCS3 in the liver increases liver insulin sensitivity in mice fed a control diet but paradoxically promotes lipogenesis, leading to the development of nonalcoholic fatty liver disease, inflammation, and obesity. (HEPATOLOGY 2010.) Obesity is associated with type 2 diabetes and the metabolic syndrome and is a major cause of morbidity and mortality.