期刊
JOURNAL OF CELL BIOLOGY
卷 190, 期 4, 页码 651-662出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201005076
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资金
- Canadian Institutes of Health Research [MOP12080]
- Canada Research Chair
- Swiss National Science Foundation [PBBSP3-127870]
- Swiss National Science Foundation (SNF) [PBBSP3-127870] Funding Source: Swiss National Science Foundation (SNF)
Mice lacking p107 exhibit a white adipose deficiency yet do not manifest the metabolic changes typical for lipodystrophy, and instead exhibit low levels of serum triglycerides and a normal liver phenotype. When fed a high fat diet, p107-null mice still did not accumulate fat in the liver, and display markedly elevated energy expenditures together with an increased energy preference for lipids. Skeletal muscle was therefore examined, as this is normally the major tissue involved in whole body lipid metabolism. Notably, p107-deficient muscle express increased levels of peroxisome proliferator-activated receptor gamma co-activator-1 alpha (PGC-1 alpha) and contained increased numbers of the pro-oxidative type I and type IIa myofibers. Chromatin immuno-precipitation revealed binding of p107 and E2F4 to the PGC-1 alpha proximal promoter, and this binding repressed promoter activity in transient transcription assays. Ectopic expression of p107 in muscle tissue in vivo results in a pronounced 20% decrease in the numbers of oxidative type IIa myofibers. Lastly, isolated p107-deficient muscle tissue display a threefold increase in lipid metabolism. Therefore, p107 determines the oxidative state of multiple tissues involved in whole body fat metabolism, including skeletal muscle.
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