In conclusion, dietary BA enhanced the growth and alleviated liver fibrosis induced by a high starch diet to steatohepatitis/recovery symptom via improving glucose and lipid metabolism, which regulated by AKT/FOXO1 and cAMP/AMPK/SREBP1 pathway in largemouth bass.
In addition, the interaction between FoxO1 and PPARγ was shown to induce hepatic steatosis in aging and db/db mice.We provide evidence that, in aged rats, FoxO1 interaction with PPARγ promotes hepatic steatosis, due to hyperglycemia-induced ER stress, which causes an impairment in Akt signaling, such in aging-related diabetes.
Zfp125 is a Foxo1-inducible transcriptional repressor that causes lipid accumulation in the AML12 mouse hepatic cell line and liver steatosis in mice by reducing liver secretion of triglycerides and hepatocyte efflux of cholesterol.
Genetic ablation of SIN3A abolishes nutrient regulation of glucokinase without affecting other FOXO1 target genes and lowers glycemia without concurrent steatosis.
Despite no changes in insulin receptor substrate (IRS)1 mRNA levels, the mRNA and protein levels of the FOXO1 target IRS2 increased progressively with the severity of steatosis from normal liver to NASH.
Overexpression of PANDER in the livers of C57Bl/6 mice promoted lipogenesis, with increased Forkhead box 1 (FOXO1) expression, whereas small interfering RNA-mediated knockdown of hepatic PANDER significantly attenuated steatosis, with reduced FOXO1 expression in db/db mice.
These data indicate that hepatic FoxO1 deregulation impairs the ability of insulin to regulate hepatic metabolism, contributing to the development of hepatic steatosis and abnormal metabolism in diabetes.