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- W631284309 abstract "This work focused on ChREBP, a master regulator of fatty acid synthesis (lipogenesis) from glucose. This metabolic pathway is stimulated by a glucose signal, via ChREBP, and by an insulin signal, via transcription factors LXR and SREBP-1c. Adenoviral expression of a constitutive active form of ChREBP (ChREBPCA) in liver was sufficient to promote lipogenesis and triglyceride accumulation (steatosis) even in a situation of SREBP-1c deficiency (insulinopenic streptozotocin (STZ) treated mice) or synergistic LXR and SREBP-1c deficiency (LXR/KO mice). Hepatic steatosis, by itself, is benign, but represents the first step of a spectrum of deleterious liver diseases (NAFLD). In STZ mice, ChREBPCA rescued the hepatic insulin signaling pathway and led to enhanced hepatic glucose storage under the form of glycogen and lipids. These mice also displayed improved glycemia, probably due to the stimulation by ChREBPCA of the insulin-sensitizer circulating factor FGF21. In contrast, expression of ChREBPCA in liver of LXR/KO mice was deleterious. Steatosis in this model was linked to inflammatory markers and to hepatocyte apoptosis. In addition, ChREBPCA, by downregulating the expression of the nuclear receptor CAR, led to an alteration in the bile acid and bilirubin detoxification pathway. In turn, accumulation of these toxic components in liver caused critical alterations in liver of LXR/KO but not in wild type mice, underlining the protective role of LXR against stressed-induced damages. These results provide novel insights on the ambivalent role of ChREBP in liver physiology, as well as on the mechanisms triggering simple steatosis transition toward more severe liver damages" @default.
- W631284309 created "2016-06-24" @default.
- W631284309 creator A5039122462 @default.
- W631284309 date "2013-01-01" @default.
- W631284309 modified "2023-09-23" @default.
- W631284309 title "ChREBP et le contrôle de la lipogenèse hépatique : interrelation avec les récepteurs nucléaires et la signalisation insulinique" @default.
- W631284309 hasPublicationYear "2013" @default.
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