It is well established that aging is associated with metabolic dysfunction such as increased adiposity and impaired energy dissipation; however, the transcriptional mechanisms regulating energy balance during late life stages have not yet been fully elucidated. Here, we show that ablation of the nuclear receptor PPAR¿ specifically in inguinal fat tissue in aging mice is associated with increased fat tissue expansion and insulin resistance. These metabolic effects are accompanied by decreased thermogenesis, reduced levels of brown fat genes, and browning of subcutaneous adipose tissue. Comparative studies of the effects of PPAR¿ downregulation in young and mid-aged mice demonstrate a preferential regulation of brown fat gene programs in inguinal fat in an age-dependent manner. In conclusion, our study uncovers an essential role for PPAR¿ in maintaining energy expenditure during the aging process and suggests the possibility of targeting PPAR¿ to counteract age-associated metabolic dysfunction.

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