Icaritin ameliorates hepatic steatosis via promoting fatty acid β-oxidation and insulin sensitivity

Aim: This study aimed to reveal the effects of icaritin (ICT) on lipotoxicity induced by palmitate (PA) in hepatic cells and steatosis in high-fat diet (HFD)-fed mice as well as exploring the potential mechanisms. Main methods: Primary mouse hepatocytes and human hepatoma Huh7 cells were used to evaluate ICT effect in vitro. HFD-fed mice were used to evaluate the ICT effect in vivo. Results: In vitro study indicated that ICT significantly rescued PA-induced steatosis, mainly through a combination of robust increased mitochondrial respiration, fatty acid oxidation and mildly decreased synthesis of fatty acid. An HFD-fed mouse model with 8 weeks HFD-fed showed metabolic disorders, while ICT application significantly reduced the weight, serum glucose levels, insulin resistance, hepatic steatosis level and adipose contents. In consistent with the observations in cell lines, ICT rescued the HFD-impaired functions and contents of key factors related to fatty acid beta-oxidation through elevated expression of peroxisome proliferator-activated receptor a (PPAR alpha). Meanwhile, it also reversed the decreased phosphoryl levels of AKT and glucogen synthase kinase 3 (GSK3 beta), leading to the improvement of insulin resistance. Significance: ICT administration had a therapeutic effect on PA- or HFD-induced hepatic steatosis and metabolic disorders. It may provide a novel strategy to construct preventive and therapeutic means for hepatic steatosis.

Automated summary

Icaritin was found to have inhibitory effects on lipotoxicity and steatosis both in vitro and in vivo, mainly through promoting fatty acid oxidation and mitochondrial respiration while reducing fatty acid synthesis. ICT also significantly alleviated metabolic disorders and hepatic steatosis induced by a high-fat diet, potentially via upregulation of PPAR alpha and modulation of AKT and GSK3 beta activity.