Department of Dental and Medical Biochemistry, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Writing Center, Hiroshima University, Higashi-Hiroshima, Japan.
Genes Cells. 2020 Apr;25(4):232-241. doi: 10.1111/gtc.12752. Epub 2020 Feb 5.
Previously, we found that the basic helix-loop-helix transcriptional repressor DEC1 interacts with the PPARγ:RXRα heterodimer, a master transcription factor for adipogenesis and lipogenesis, to suppress transcription from PPARγ target genes (Noshiro et al., Genes to Cells, 2018, 23:658-669). Because the expression of PPARγ and several of its target genes exhibits circadian rhythmicity in white adipose tissue (WAT), we examined the expression profiles of PPARγ target genes in wild-type and Dec1 mice. We found that the expression of PPARγ 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 PPARγ:RXRα and DEC1 cooperatively generate the circadian expression of PPARγ target genes through PPAR-responsive elements in WAT.
先前，我们发现基本螺旋-环-螺旋转录阻遏物 DEC1 与 PPARγ:RXRα 异二聚体相互作用，PPARγ:RXRα 异二聚体是脂肪生成和脂生成的主转录因子，可抑制 PPARγ 靶基因的转录（Noshiro 等人，《基因与细胞》，2018，23：658-669）。由于 PPARγ 和其几个靶基因的表达在白色脂肪组织（WAT）中呈现昼夜节律性，我们检查了野生型和 Dec1 小鼠中 PPARγ 靶基因的表达谱。我们发现，负责脂质代谢的 PPARγ 靶基因的表达，包括从游离脂肪酸（FFAs）合成三酰基甘油、脂质储存和三酰基甘油分解为 FFAs，在 WAT 中呈昼夜节律性波动。此外，DEC1 缺乏导致这些基因在夜间（ Zeitgeber 时间 16 和 22）的表达显著增加，导致昼夜节律紊乱。野生型小鼠的血清 FFA 水平也呈现昼夜波动，但 DEC1 缺乏会破坏这些波动，导致 FFA 水平降低。这些结果表明，PPARγ:RXRα 和 DEC1 通过 WAT 中的 PPAR 反应元件协同产生 PPARγ 靶基因的昼夜表达。
