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Article Dans Une Revue Scientific Reports Année : 2019

The Differential Expression of Cide Family Members is Associated with Nafld Progression from Steatosis to Steatohepatitis

Arnaud Sans
  • Fonction : Auteur
Xu Xu
Ann-Hwee Lee
  • Fonction : Auteur
Kaori Minehira
  • Fonction : Auteur

Résumé

Improved understanding of the molecular mechanisms responsible for the progression from a “non-pathogenic” steatotic state to Non-Alcoholic Steatohepatitis is an important clinical requirement. The cell death-inducing DFF45 like effector (CIDE) family members (A, B and FSP27) regulate hepatic lipid homeostasis by controlling lipid droplet growth and/or VLDL production. However, CIDE proteins, particularly FSP27, have a dual role in that they also regulate cell death. We here report that the hepatic expression of CIDEA and FSP27 (α/β) was similarly upregulated in a dietary mouse model of obesity-mediated hepatic steatosis. In contrast, CIDEA expression decreased, but FSP27-β expression strongly increased in a dietary mouse model of steatohepatitis. The inverse expression pattern of CIDEA and FSP27β was amplified with the increasing severity of the liver inflammation and injury. In obese patients, the hepatic CIDEC2 (human homologue of mouse FSP27β) expression strongly correlated with the NAFLD activity score and liver injury. The hepatic expression of CIDEA tended to increase with obesity, but decreased with NAFLD severity. In hepatic cell lines, the downregulation of FSP27β resulted in the fractionation of lipid droplets, whereas its overexpression decreased the expression of the anti-apoptotic BCL2 marker. This, in turn, sensitized cells to apoptosis in response to TNF α and saturated fatty acid. Considered together, our animal, human and in vitro studies indicate that differential expression of FSP27β/CIDEC2 and CIDEA is related to NAFLD progression and liver injury.
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hal-04496701 , version 1 (26-06-2024)

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Arnaud Sans, Stéphanie Bonnafous, Déborah Rousseau, Stéphanie Patouraux, Clémence Canivet, et al.. The Differential Expression of Cide Family Members is Associated with Nafld Progression from Steatosis to Steatohepatitis. Scientific Reports, 2019, 9 (1), pp.7501. ⟨10.1038/s41598-019-43928-7⟩. ⟨hal-04496701⟩
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