Dec1 Regulates The Rhythmic Expression Of Ppar Gamma Target Genes Involved In Lipid Metabolism In White Adipose Tissue

Previously, we found that the basic helix-loop-helix transcriptional repressor DEC1 interacts with the PPAR gamma:RXR alpha heterodimer, a master transcription factor for adipogenesis and lipogenesis, to suppress transcription from PPAR gamma target genes (Noshiro et al., Genes to Cells, 2018, 23:658-669). Because the expression of PPAR gamma and several of its target genes exhibits circadian rhythmicity in white adipose tissue (WAT), we examined the expression profiles of PPAR gamma target genes in wild-type and Dec1(-/-) mice. We found that the expression of PPAR gamma target genes responsible for lipid metabolism, including the synthesis of triacylglycerol from free fatty acids (FFAs), lipid storage and the lipolysis of triacylglycerol to FFAs, oscillates in a circadian manner in WAT. Moreover, DEC1 deficiency led to a marked increase in the expression of these genes at night (Zeitgeber times 16 and 22), resulting in disruption of circadian rhythms. Serum FFA levels in wild-type mice also showed circadian oscillations, but these were disrupted by DEC1 deficiency, leading to reduced FFA levels. These results suggest that PPAR gamma:RXR alpha and DEC1 cooperatively generate the circadian expression of PPAR gamma target genes through PPAR-responsive elements in WAT.