biostudies-literatureWang HNIH HHS1468https://www.ebi.ac.uk/biostudies/studies/S-EPMC12898518biostudies-literatureUnknown27(3)Forkhead box protein A3 (FOXA3), also known as hepatocyte nuclear factor 3g (HNF3g), is a member of the FOX family of transcription factors and regulates lipid and glucose metabolism and liver regeneration. Hepatic FOXA3 is reduced in obesity and patients with metabolic dysfunction-associated steatohepatitis (MASH). So far, it remains unknown whether hepatic FOXA3 is essential for regulating lipid metabolism or metabolic dysfunction-associated liver disease (MASLD). In this study, we first investigated whether genetic inactivation of hepatocyte <i>Foxa3</i> affected the development of MASLD/MASH in C57BL/6 mice and then explored whether loss of hepatocyte <i>Foxa3</i> regulated atherosclerosis development in <i>Ldlr</i>-deficient mice. Inactivation of <i>Foxa3</i> in hepatocytes did not afInternational journal of molecular sciencesLoss of Hepatocyte FOXA3 Improves MASH and Atherosclerosis in Hyperlipidemic Ldlr-Deficient Mice.PMC128985181R01DK121548-041R01DK118805-04Gopoju RHu SGunawardana LZhang YWang HWang XWang JLin LYin LfalseLoss of Hepatocyte FOXA3 Improves MASH and Atherosclerosis in Hyperlipidemic Ldlr-Deficient Mice.Forkhead box protein A3 (FOXA3), also known as hepatocyte nuclear factor 3g (HNF3g), is a member of the FOX family of transcription factors and regulates lipid and glucose metabolism and liver regeneration. Hepatic FOXA3 is reduced in obesity and patients with metabolic dysfunction-associated steatohepatitis (MASH). So far, it remains unknown whether hepatic FOXA3 is essential for regulating lipid metabolism or metabolic dysfunction-associated liver disease (MASLD). In this study, we first investigated whether genetic inactivation of hepatocyte <i>Foxa3</i> affected the development of MASLD/MASH in C57BL/6 mice and then explored whether loss of hepatocyte <i>Foxa3</i> regulated atherosclerosis development in <i>Ldlr</i>-deficient mice. Inactivation of <i>Foxa3</i> in hepatocytes did not af2026-01-01T00:00:00Z2026 Feb2026-07-09T10:21:29.211Z2026-07-09T10:18:54.959ZS-EPMC128985184168388910.3390/ijms27031468