Downregulation of Hepatic PPA1 Protects Against Obesity by Elevating FGF21 Production via eIF2α Phosphorylation

Pyrophosphatase 1 (PPA1) is upregulated in livers of high-fat diet-induced obese mice and metabolic dysfunction-associated steatotic liver disease patients. Hepatic PPA1 deletion protects mice against high-fat diet-induced obesity and related metabolic disorders by promoting whole-body energy expenditure. Deficiency of hepatic PPA1 expression facilitates fibroblast growth factor 21 production by activating the GCN2/eIF2α/ATF4 signaling pathway.