期刊
MOLECULAR ENDOCRINOLOGY
卷 20, 期 5, 页码 1138-1152出版社
OXFORD UNIV PRESS INC
DOI: 10.1210/me.2005-0407
关键词
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资金
- NIDDK NIH HHS [DK59820] Funding Source: Medline
Members of the steroid receptor coactivator (SRC) family, which include SRC-1 (NcoA-1/p160), SRC2(TIF2/GRIP1/NcoA-2) and SRC-3(pCIP/RAC3/ACTR/pCIP/AIB1/TRAM1), are critical mediators of steroid receptor action. Gene ablation studies previously identified SRC-1 and SRC-2 as being involved in the control of energy homeostasis. A more precise identification of the molecular pathways regulated by these coactivators is crucial for understanding the role of steroid receptor coactivators in the control of energy homeostasis and obesity. A genomic approach using microarray analysis was employed to identify the subsets of genes that are altered in the livers of SRC-1(-/-), SRC-2(-/-), and SRC-3(-/-) mice. Microarray analysis demonstrates that gene expression changes are specific and nonoverlapping for each SRC member in the liver. The overall pattern of altered gene expressions in the SRC-1(-/-) mice was upregulation, whereas SRC-2(-/-) mice showed an overall down-regulation. Several key regulatory enzymes of energy metabolism were significantly altered in the liver of SRC-2(-/-) mice, which are consistent with the prior observation that SRC2(-/-) mice have increased energy expenditure. This study demonstrates that the molecular targets of SRC-2 regulation in the murine liver stimulate fatty acid degradation and glycolytic pathway, whereas fatty acid, cholesterol, and steroid biosynthetic pathways are down-regulated.
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