REV-ERBα Activates C/EBP Homologous Protein to Control Small Heterodimer Partner–Mediated Oscillation of Alcoholic Fatty Liver

Sep 25, 2016The American journal of pathology

REV-ERBα triggers a stress protein to regulate small heterodimer partner-driven cycles in alcoholic fatty liver

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Abstract

ED+E induced steatosis in wild-type mice, marked by increased ATF4 and decreased CHOP and SREBP-1c.

  • Distinct variations in serum and liver lipid profiles were observed in wild-type and Shpmice after ethanol exposure.
  • Wild-type mice showed steatosis with increased expression of ATF4 and decreased levels of CHOP and SREBP-1c.
  • In contrast, Shpmice exhibited lipid accumulation after a control diet, marked by elevated CHOP, SREBP-1c, and REV-ERBα, but reduced ATF4.
  • REV-ERBα was found to activate the CHOP promoter and gene transcription, a process inhibited by SHP.
  • Knockdown of Rev-Erbα in Shpmice prevented steatosis associated with ethanol exposure.

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