Journal Article

Foxa2 attenuates steatosis and inhibits the NF-κB/IKK signaling pathway in nonalcoholic fatty liver disease

Yang, Li, Ma, Qiang, Kong, Xiangcai, Yu, Xiaohui, Wang, Wei, Chen, Jiayu

2023

Overview

Forkhead box a2 (Foxa2) is proven to be an insulin-sensitive transcriptional regulator and affects hepatic steatosis. This study aims to investigate the mechanism by which Foxa2 affects nonalcoholic fatty liver disease (NAFLD). Animal and cellular models of NAFLD were constructed using high-fat diet (HFD) feeding and oleic acid (OA) stimulation, respectively. NAFLD mice received tail vein injections of either an overexpressing negative control (oe-NC) or Foxa2 (oe-Foxa2) for four weeks. HepG2 cells were transfected with oe-NC and oe-Foxa2 for 48 h before OA stimulation. Histological changes and lipid accumulation were assessed using hematoxylin-eosin staining and oil red O staining, respectively. Expression of Foxa2, NF-κB/IKK pathway proteins, lipid synthesis proteins, and fatty acid β-oxidation protein in HFD mice and OA-induced HepG2 cells was detected using western blot. Foxa2 expression was downregulated in HFD mice and OA-induced HepG2 cells. Foxa2 overexpression attenuated lipid accumulation and liver injury, and reduced the levels of aspartate aminotransferase, alanine aminotransferase, total cholesterol, or triglyceride in HFD mice and OA-induced HepG2 cells. Moreover, Foxa2 overexpression decreased the expression of lipid synthesis proteins and increased fatty acid β-oxidation protein expression in the liver tissues. Furthermore, overexpression of Foxa2 downregulated the expression of p-NF-κB/NF-κB and p-IKK/IKK in OA-induced HepG2 cells. Additionally, lipopolysaccharide (NF-κB/IKK pathway activator) administration reversed the downregulation of lipid synthesis proteins and the upregulation of fatty acid β-oxidation protein. Foxa2 expression is downregulated in NAFLD. Foxa2 ameliorated hepatic steatosis and inhibited the activation of the NF-κB/IKK signaling pathway.

• Publisher: PeerJ, Inc,PeerJ Inc
• Subject: Alanine transaminase / Animal models / Animals / Aspartate aminotransferase / Cell Biology / Cholesterol / Down-regulation / Fatty acids / Fatty liver / Forkhead box a2 / Forkhead protein / Gastroenterology and Hepatology / Hepatic steatosis / Hepatocyte Nuclear Factor 3-beta - genetics / High fat diet / Inflammation / Insulin resistance / Lipids / Lipopolysaccharides / Liver diseases / Metabolism / Mice / NF-kappa B - metabolism / NF-κB protein / NF-κB/IKK signaling pathway / Non-alcoholic Fatty Liver Disease - genetics / Nonalcoholic fatty liver disease / Oleic acid / Oleic Acid - pharmacology / Oxidation / Phosphorylation / Proteins / Reagents / Signal Transduction / Steatosis