A Functional Interaction between RIP140 and PGC-1α Regulates the Expression of the Lipid Droplet Protein CIDEA

Nuclear receptors activate or repress target genes depending on the recruitment of coactivators or corepressors. The corepressor RIP140 and the PPAR coactivator 1 alpha (PGC-1 alpha) both play key roles in the regulated transcription of genes involved in energy homeostasis. We investigated the roles of RIP140 and PGC-1 alpha in controlling the expression of CIDEA, an important regulatory factor in adipose cell function and obesity. Ectopically expressed CIDEA surrounded lipid droplets in brown adipocytes and induced the formation of lipid droplets in nonadipogenic cell lines. The expression and promoter activity of CIDEA was repressed by RIP140 and induced by PGC-1 alpha, mediated through the binding of estrogen-related receptor alpha and NRF-1 to their cognate binding sites. Importantly, we demonstrate that RIP140 interacts directly with PGC-1 alpha and suppresses its activity. The direct antagonism of PGC-1 alpha by RIP140 provides a mechanism for regulating target gene transcription via nuclear receptor-dependent and -independent pathways.