Hepatic glucose production rises with the histological severity of metabolic dysfunction-associated steatohepatitis.

ABSTRACT: Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are associated with a high prevalence of type 2 diabetes (T2D). Individuals with MASLD exhibit insulin resistance (IR) and hyperglycemia, but it is unclear whether hepatic glucose production (HGP) is increased with MASLD severity. We evaluated HGP in a cohort of histologically characterized individuals with MASL/MASH using stable isotope infusion (6,6-²H₂-glucose, U-²H₅-glycerol) and liver-specific genome-scale metabolic models (GEMs). Tracer-measured HGP is increased with liver fibrosis and inflammation, but not steatosis, and is associated with lipolysis and IR. The GEM-derived gluconeogenesis is elevated due to high glucogenic/energy metabolite uptakes

SUBMITTER: Sabatini S 

PROVIDER: S-EPMC11604487 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature