Nuclear Receptor Cofactors in PPARgamma-Mediated Adipogenesis and Adipocyte Energy Metabolism

Abstract

Transcriptional cofactors are integral to the proper function and regulation of nuclear receptors. Members of the peroxisome proliferator-activated receptor (PPAR) family of nuclear receptors are involved in the regulation of lipid and carbohydrate metabolism. They modulate gene transcription in response to a wide variety of ligands, a process that is mediated by transcriptional coactivators and corepressors. The mechanisms by which these cofactors mediate transcriptional regulation of nuclear receptor function are still being elucidated. The rapidly increasing array of cofactors has brought into focus the need for a clear understanding of how these cofactors interact in ligand- and cell-specific manners. This review highlights the differential effects of the assorted cofactors regulating the transcriptional action of PPARgamma and summarizes the recent advances in understanding the physiological functions of corepressors and coactivators.

Figure 1

Putative functions of PPARγ cofactors in white adipose- and brown adipose-modulated lipid and energy metabolism. Positive regulators are highlighted in red. Preadipocytes can be differentiated into white adipocytes via transcriptional regulation of PPARγ by coactivators CBP and TRAP220, or differentiated into brown adipocytes via transactivation by PGC-1β, PGC-1α, and SRC-1. TIF2 plays roles in lipid storage from white adipocytes, while p/CIP and SRC-1 function to promote lipid storage in brown fat. PGC-1α is not only involved in adaptive thermogenesis but it also promotes the conversion of white adipocytes into brown adipocytes. SRC-1 is the only member of p160 proteins that show clear function in energy expenditure.