Morris White, PhD

Follistatin mediates MASLD and MASH during hepatic insulin resistance on a high fructose diet

MASLD (metabolic dysfunction-associated steatotic liver disease) and its progression to steatohepatitis (MASH) correlates with IR (insulin resistance). However, mice with complete hepatic IR owing to hepatic disruption of Irs1 and Irs2 (LDKO mice) develop diabetes without MASLD when fed chow or high-fat diets. During this seminar, I will we show that LDKO mice fed the fructose-enriched GAN diet developed acute MASLD/MASH–despite impaired hepatic lipogenesis. We infer that fructose-derived glycerol-3-phosphate synergized with Fst promoted adipose lipolysis, causing MASLD through hepatic fatty acid re-esterification.

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Professor of Pediatrics, Boston Children’s Hospital, Boston MA