CCAAT/Enhancer-binding Protein β Deletion Reduces Adiposity, Hepatic Steatosis, and Diabetes in Leprdb/db Mice

作者: Jill M. Schroeder-Gloeckler , Shaikh Mizanoor Rahman , Rachel C. Janssen , Liping Qiao , Jianhua Shao

DOI: 10.1074/JBC.M701329200

关键词:

摘要: CCAAT/enhancer-binding protein beta (C/EBPbeta) plays a key role in initiation of adipogenesis adipose tissue and gluconeogenesis liver; however, the C/EBPbeta hepatic lipogenesis remains undefined. Here we show that inactivation Lepr(db/db) mice attenuates obesity, fatty liver, diabetes. In addition to impaired adipogenesis, livers from C/EBPbeta(-/-) x had dramatically decreased triglyceride content reduced lipogenic enzyme activity. deletion down-regulated peroxisome proliferator-activated receptor gamma2 (PPARgamma2) stearoyl-CoA desaturase-1 up-regulated PPARalpha independent SREBP1c. Conversely, overexpression wild-type increased PPARgamma2 mRNA content. FAO cells, liver inhibiting form or RNA interference attenuated palmitate-induced accumulation levels vivo. Leptin anti-diabetic drug metformin acutely expression hepatocytes, whereas acids up-regulate expression. These data provide novel evidence linking energy balance with important implications for treatment obesity disease.

参考文章(88)
Isabella Screpanti, Luigina Romani, Piero Musiani, Andrea Modesti, E Fattori, D Lazzaro, C Sellitto, Susanna Scarpa, Diana Bellavia, G Lattanzio, None, Lymphoproliferative disorder and imbalanced T-helper response in C/EBP beta-deficient mice. The EMBO Journal. ,vol. 14, pp. 1932- 1941 ,(1995) , 10.1002/J.1460-2075.1995.TB07185.X
Roshanak Rahimian, Esther Masih‐Khan, Maggie Lo, Cornelis van Breemen, Bruce M. McManus, Gregory P. Dubé, Hepatic over-expression of peroxisome proliferator activated receptor gamma2 in the ob/ob mouse model of non-insulin dependent diabetes mellitus. Molecular and Cellular Biochemistry. ,vol. 224, pp. 29- 37 ,(2001) , 10.1023/A:1011927113563
Stephen M. Taubenfeld, Maria H. Milekic, Barbara Monti, Cristina M. Alberini, The consolidation of new but not reactivated memory requires hippocampal C/EBPβ Nature Neuroscience. ,vol. 4, pp. 813- 818 ,(2001) , 10.1038/90520
Michael W. Schwartz, Stephen C. Woods, Daniel Porte, Randy J. Seeley, Denis G. Baskin, Central nervous system control of food intake Nature. ,vol. 404, pp. 661- 671 ,(2000) , 10.1038/35007534
Carl M. Nepokroeff, M.R. Lakshmanan, John W. Porter, Fatty-acid synthase from rat liver. Methods in Enzymology. ,vol. 35, pp. 37- 44 ,(1975) , 10.1016/0076-6879(75)35136-7
Jiandie Lin, Christoph Handschin, Bruce M. Spiegelman, Metabolic control through the PGC-1 family of transcription coactivators. Cell Metabolism. ,vol. 1, pp. 361- 370 ,(2005) , 10.1016/J.CMET.2005.05.004
Sha Liu, Colleen Croniger, Carmen Arizmendi, Mariko Harada-Shiba, Jianming Ren, Valeria Poli, Richard W. Hanson, Jacob E. Friedman, Hypoglycemia and impaired hepatic glucose production in mice with a deletion of the C/EBPβ gene Journal of Clinical Investigation. ,vol. 103, pp. 207- 213 ,(1999) , 10.1172/JCI4243