title: CCAAT/enhancer-binding protein beta deletion reduces adiposity, hepatic steatosis, and diabetes in Lepr(db/db) mice.
abstract: 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.
authors: Department of Pediatrics, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado 80045, USA.
authors: Jill M
authors: JM
authors: Schroeder-Gloeckler
authors: Shaikh Mizanoor
authors: SM
authors: Rahman
authors: Rachel C
authors: RC
authors: Janssen
authors: Liping
authors: L
authors: Qiao
authors: Jianhua
authors: J
authors: Shao
authors: Michael
authors: M
authors: Roper
authors: Stephanie J
authors: SJ
authors: Fischer
authors: Erin
authors: E
authors: Lowe
authors: David J
authors: DJ
authors: Orlicky
authors: James L
authors: JL
authors: McManaman
authors: Carol
authors: C
authors: Palmer
authors: William L
authors: WL
authors: Gitomer
authors: Wan
authors: W
authors: Huang
authors: Robert M
authors: RM
authors: O'Doherty
authors: Thomas C
authors: TC
authors: Becker
authors: Dwight J
authors: DJ
authors: Klemm
authors: Dalan R
authors: DR
authors: Jensen
authors: Leslie K
authors: LK
authors: Pulawa
authors: Robert H
authors: RH
authors: Eckel
authors: Jacob E
authors: JE
authors: Friedman
mesh_terms: D050154:Adiposity / Q000187:drug effects / Q000235:genetics; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000172:deficiency / Q000378:metabolism*; D002460:Cell Line; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008687:Metformin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D047493:PPAR alpha / Q000096:biosynthesis; D047495:PPAR gamma / Q000096:biosynthesis; D010168:Palmitates / Q000494:pharmacology; D013230:Stearoyl-CoA Desaturase / Q000096:biosynthesis; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis; D014280:Triglycerides / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D007004:Hypoglycemic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D010168:Palmitates; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014280:Triglycerides; D008687:Metformin; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase