期刊
CELL METABOLISM
卷 15, 期 1, 页码 51-64出版社
CELL PRESS
DOI: 10.1016/j.cmet.2011.12.006
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ono Medical Research Foundation
- Uehara Memorial Foundation
- Daiichi-Sankyo Foundation of Life Science
- NOVARTIS Foundation for the Promotion Science
- Japan Diabetes Foundation
- Mitsui Life Social Welfare Foundation
- Naito Foundation
- Japanese Society of Anti-Aging Medicine
- Mitsubishi Pharma Research Foundation
- Ministry of Education, Science, Sports, and Culture and Health and Labor Sciences
- Ministry of Education, Science, Sports, and Culture, and Health
- Takeda Science Foundation
- Kowa Life Science Foundation
- Grants-in-Aid for Scientific Research [24390195, 21390237, 23790833] Funding Source: KAKEN
- Austrian Science Fund (FWF) [F 3002, Z 136] Funding Source: researchfish
Several clinical studies have shown that insulin resistance is prevalent among patients with heart failure, but the underlying mechanisms have not been fully elucidated. Here, we report a mechanism of insulin resistance associated with heart failure that involves upregulation of p53 in adipose tissue. We found that pressure overload markedly upregulated p53 expression in adipose tissue along with an increase of adipose tissue inflammation. Chronic pressure overload accelerated lipolysis in adipose tissue. In the presence of pressure overload, inhibition of lipolysis by sympathetic denervation significantly downregulated adipose p53 expression and inflammation, thereby improving insulin resistance. Likewise, disruption of p53 activation in adipose tissue attenuated inflammation and improved insulin resistance but also ameliorated cardiac dysfunction induced by chronic pressure overload. These results indicate that chronic pressure overload upregulates adipose tissue p53 by promoting lipolysis via the sympathetic nervous system, leading to an inflammatory response of adipose tissue and insulin resistance.
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