1,3-Dichloro-2-propanol Causes Lipid Droplet Accumulation by Inhibiting Autophagy via REV-ERBα in Hepatocytes

1,3-Dichloro-2-propanol (1,3-DCP), a food processing contaminant, induces hepatic lipid accumulation through unclear mechanisms. The circadian clock system plays a central role in regulating cellular metabolism. This study investigated the exact mechanisms underlying 1,3-DCP-induced lipid droplet (LD) accumulation and the potential regulatory role of the circadian clock. Results showed that 1,3-DCP induced LD accumulation by inhibiting autophagy. Further studies revealed that 1,3-DCP disrupted the circadian oscillations of circadian clock core components REV-ERBα, BMAL1, and CLOCK and upregulated REV-ERBα expression. 1,3-DCP also disrupted the rhythmic expression of autophagy proteins mTOR, BECN1, LC3, and p62. Silencing REV-ERBα significantly alleviated 1,3-DCP-induced autophagy dysfunction and LD accumulation. Overall, our results indicated that 1,3-DCP induced REV-ERBα-mediated autophagic impairment through disrupting the circadian clock, ultimately inducing LD accumulation. The circadian clock-autophagy pathway may represent a novel mechanism for LD accumulation. Our study elucidated the precise mechanism underlying 1,3-DCP-induced LD accumulation and identified REV-ERBα as a promising therapeutic target.