CCAAT/Enhancer-binding Protein β Deletion Reduces Adiposity, Hepatic Steatosis, and Diabetes in Lepr Mice
Copyright policy )CCAAT/Enhancer-binding Protein β Deletion Reduces Adiposity, Hepatic Steatosis, and Diabetes in Lepr Mice
CCAAT/enhancer-binding protein beta (C/EBPbeta) plays a key role in initiation of adipogenesis in adipose tissue and gluconeogenesis in liver; however, the role of C/EBPbeta in hepatic lipogenesis remains undefined. Here we show that C/EBPbeta inactivation in Lepr(db/db) mice attenuates obesity, fatty liver, and diabetes. In addition to impaired adipogenesis, livers from C/EBPbeta(-/-) x Lepr(db/db) mice had dramatically decreased triglyceride content and reduced lipogenic enzyme activity. C/EBPbeta deletion in Lepr(db/db) mice down-regulated peroxisome proliferator-activated receptor gamma2 (PPARgamma2) and stearoyl-CoA desaturase-1 and up-regulated PPARalpha independent of SREBP1c. Conversely, C/EBPbeta overexpression in wild-type mice increased PPARgamma2 and stearoyl-CoA desaturase-1 mRNA and hepatic triglyceride content. In FAO cells, overexpression of the liver inhibiting form of C/EBPbeta or C/EBPbeta RNA interference attenuated palmitate-induced triglyceride accumulation and reduced PPARgamma2 and triglyceride levels in the liver in vivo. Leptin and the anti-diabetic drug metformin acutely down-regulated C/EBPbeta expression in hepatocytes, whereas fatty acids up-regulate C/EBPbeta expression. These data provide novel evidence linking C/EBPbeta expression to lipogenesis and energy balance with important implications for the treatment of obesity and fatty liver disease.
- University of Colorado System United States
- University of Colorado Denver United States
- Duke University Health System United States
- Veterans Health Administration United States
- Duke Medical Center United States
Mice, Knockout, CCAAT-Enhancer-Binding Protein-beta, Palmitates, Metformin, Cell Line, Fatty Liver, PPAR gamma, Mice, Gene Expression Regulation, Diabetes Mellitus, Animals, Hypoglycemic Agents, PPAR alpha, Obesity, Energy Metabolism, Sterol Regulatory Element Binding Protein 1, Stearoyl-CoA Desaturase, Triglycerides, Adiposity
Mice, Knockout, CCAAT-Enhancer-Binding Protein-beta, Palmitates, Metformin, Cell Line, Fatty Liver, PPAR gamma, Mice, Gene Expression Regulation, Diabetes Mellitus, Animals, Hypoglycemic Agents, PPAR alpha, Obesity, Energy Metabolism, Sterol Regulatory Element Binding Protein 1, Stearoyl-CoA Desaturase, Triglycerides, Adiposity
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