Suppression of insulin-induced gene 1 (INSIG1) function promotes hepatic lipid remodelling and restrains NASH progression.

One day after CCl 4 injection, the Insig1 Het and KO mice showed a trend of reduced hepatotoxicity (ALT, Figure S3A ) compared to their WT littermates and this trend flattened on day four after the challenge (ALT, Figure S3B ).

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Overall, an enhanced remodelling of the lipidome toward desaturated lipids is expected to reduce lipotoxicity in murine models of NASH [ 28 ]; accordingly, the Insig1 KO mice showed reduced hepatocyte damage with ALT values below the upper limit of normal ( Figure S2P ) which, although “clinically” significant, did not reach statistical significance.

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