PER2 controls lipid metabolism by direct regulation of PPARγ

Benedetto Grimaldi, Marina Maria Bellet, Sayako Katada, Giuseppe Astarita, Jun Hirayama, Rajesh H. Amin, James G. Granneman, Daniele Piomelli, Todd Leff, Paolo Sassone-Corsi

研究成果: Contribution to journalArticle査読

290 被引用数 (Scopus)

抄録

Accumulating evidence highlights intriguing interplays between circadian and metabolic pathways. We show that PER2 directly and specifically represses PPARγ, a nuclear receptor critical in adipogenesis, insulin sensitivity, and inflammatory response. PER2-deficient mice display altered lipid metabolism with drastic reduction of total triacylglycerol and nonesterified fatty acids. PER2 exerts its inhibitory function by blocking PPARγ recruitment to target promoters and thereby transcriptional activation. Whole-genome microarray profiling demonstrates that PER2 dictates the specificity of PPARγ transcriptional activity. Indeed, lack of PER2 results in enhanced adipocyte differentiation of cultured fibroblasts. PER2 targets S112 in PPARγ, a residue whose mutation has been associated with altered lipid metabolism. Lipidomic profiling demonstrates that PER2 is necessary for normal lipid metabolism in white adipocyte tissue. Our findings support a scenario in which PER2 controls the proadipogenic activity of PPARγ by operating as its natural modulator, thereby revealing potential avenues of pharmacological and therapeutic intervention.

本文言語英語
ページ(範囲)509-520
ページ数12
ジャーナルCell metabolism
12
5
DOI
出版ステータス出版済み - 11 3 2010
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生理学
  • 分子生物学
  • 細胞生物学

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