Fructose and follistatin potentiate acute MASLD during complete hepatic insulin resistance.

ABSTRACT: MASLD (metabolic-associated steatotic liver disease) and MASH (steatohepatitis) are closely associated with hepatic IR (insulin resistance) and T2D. Regardless, insulin-stimulated hepatic lipogenesis is considered essential for MASLD development, as mouse models of complete hepatic IR become diabetic without MASLD when fed high-fat diets. Challenging this notion, we found that male LDKO mice lacking hepatic insulin receptor substrates acutely developed MASLD if fed a fructose-enriched "MASH diet" (GAN) or high-fructose diet. Fructose potentiated hepatic re-esterification of abundant circulating fatty acids in LDKO mice, evidenced by excess ¹³C incorporation into the glycerol backbone-but not fatty acid chains-of hepatic triacylglyceride after gavage with [U¹³C]fructos

SUBMITTER: Tao R 

PROVIDER: S-EPMC12749807 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature