CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Schroeder-Gloeckler, JM; Rahman, SM; Janssen, RC; Qiao, L; Shao, J; Roper, M; Fischer, SJ; Lowe, E; Orlicky, DJ; McManaman, JL; Palmer, C; Gitomer, WL; Huang, W; O'Doherty, RM; Becker, TC; Klemm, DJ; Jensen, DR; Pulawa, LK; Eckel, RH; Friedman, JE

Published Date

  • May 25, 2007

Published In

Volume / Issue

  • 282 / 21

Start / End Page

  • 15717 - 15729

PubMed ID

  • 17387171

Pubmed Central ID

  • 17387171

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M701329200

Language

  • eng

Conference Location

  • United States