Liver gene expression and its rewiring in hepatic steatosis are controlled by PI3Kα-dependent hepatocyte signaling.

ABSTRACT: Insulin and other growth factors are key regulators of liver gene expression, including in metabolic diseases. Most of the phosphoinositide 3-kinase (PI3K) activity induced by insulin is considered to be dependent on PI3Kα. We used mice lacking p110α, the catalytic subunit of PI3Kα, to investigate its role in the regulation of liver gene expression in health and in metabolic dysfunction-associated steatotic liver disease (MASLD). The absence of hepatocyte PI3Kα reduced maximal insulin-induced PI3K activity and signaling, promoted glucose intolerance in lean mice and significantly regulated liver gene expression, including insulin-sensitive genes, in ad libitum feeding. Some of the defective regulation of gene expression in response to hepatocyte-restricted insulin receptor deletion was rel

SUBMITTER: Regnier M 

PROVIDER: S-EPMC12021288 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature