期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 282, 期 21, 页码 15717-15729出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M701329200
关键词
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资金
- NICHD NIH HHS [HD-38129, R01 HD045965, HD-045962, P01 HD038129, U10 HD045962] Funding Source: Medline
- NIDDK NIH HHS [DK59767, U01-DK-56047, DK-072162, R01 DK053969, DK-53969, R01 DK072162, R01 DK059767, P30 DK048520, R01 DK026356, P30-DK-48520, DK-26356, DK-058855, R01 DK058855] Funding Source: Medline
CCAAT/enhancer-binding protein beta (C/EBP beta) plays a key role in initiation of adipogenesis in adipose tissue and gluconeogenesis in liver; however, the role of C/ EBP beta in hepatic lipogenesis remains undefined. Here we show that C/EBP beta inactivation in Leprdb/ db mice attenuates obesity, fatty liver, and diabetes. In addition to impaired adipogenesis, livers from C/EB beta(-/-) x Lepr(db/db) mice had dramatically decreased triglyceride content and reduced lipogenic enzyme activity. C/EBP beta deletion in Lepr(db/db) mice down-regulated peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2) and stearoyl-CoA desaturase-1 and up-regulated PPAR alpha independent of SREBP1c. Conversely, C/EBP beta overexpression in wild-type mice increased PPAR gamma 2 and stearoyl-CoA desaturase-1 mRNA and hepatic triglyceride content. In FAO cells, overexpression of the liver inhibiting form of C/EBP beta or C/EBP beta RNA interference attenuated palmitate-induced triglyceride accumulation and reduced PPAR gamma 2 and triglyceride levels in the liver in vivo. Leptin and the anti-diabetic drug metformin acutely down-regulated C/EBP beta expression in hepatocytes, whereas fatty acids up-regulate C/EBP beta expression. These data provide novel evidence linking C/EBP beta expression to lipogenesis and energy balance with important implications for the treatment of obesity and fatty liver disease.
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