Hepatocyte nuclear factor 4α in the pathogenesis of non-alcoholic fatty liver disease

Abstract

Non-alcoholic fatty liver disease (NAFLD) is emerging as the most common chronic liver disease worldwide. It refers to a range of liver conditions affecting people who drink little or no alcohol. NAFLD comprises non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH), the more aggressive form of NAFLD. NASH is featured by steatosis, lobular inflammation, hepatocyte injury, and various degrees of fibrosis. Although much progress has been made over the past decades, the pathogenic mechanism of NAFLD remains to be fully elucidated. Hepatocyte nuclear factor 4α (HNF4α) is a nuclear hormone receptor that is highly expressed in hepatocytes. Hepatic HNF4α expression is markedly reduced in NAFLD patients and mouse models of NASH. HNF4α has been shown to regulate bile acid, lipid, glucose, and drug metabolism. In this review, we summarize the recent advances in the understanding of the pathogenesis of NAFLD with a focus on the regulation of HNF4α and the role of hepatic HNF4α in NAFLD. Several lines of evidence have shown that hepatic HNF4α plays a key role in the initiation and progression of NAFLD. Recent data suggest that hepatic HNF4α may be a promising target for treatment of NAFLD.

Hepatic retinoic acid receptor alpha mediates all‐trans retinoic acid's effect on diet‐induced hepatosteatosis

“…Hepatic retinoic acid receptor alpha mediates all-trans retinoic acid's effect on diet-induced hepatosteatosis Fathima N. Cassim Bawa 1,2 | Yanyong Xu 2 | Raja Gopoju 2 | Noel-Marie Plonski 1 | Amy Shiyab 1,2 | Shuwei Hu 2 | Shaoru Chen 2 | Yingdong Zhu 1,2 | Kavita Jadhav 1,2 | Takhar Kasumov 3 | Yanqiao Zhang 2 cells (HSCs). When HSCs are activated, -they lose the retinyl ester stores, leading to fibrosis.…”

“…During insulin resistance, hepatic de novo lipogenesis and fatty acid uptake are increased to induce hepatosteatosis and lipotoxic lipid accumulation, which may further cause liver inflammation and fibrogenesis. [1][2][3] Vitamin A is important for many biological processes, such as embryogenesis, cell proliferation and differentiation, vision, immune regulation, and metabolism. [4] Patients with NAFLD have often shown disrupted vitamin A homeostasis.…”

Metabolic dysfunction-associated fatty liver disease: from basic research to clinical application

“…Although a great deal of progress has been made in recent decades, the pathogenic mechanism of NAFLD/MAFLD has yet to be fully elucidated. In this issue of the Chinese Medical Journal ( CMJ ), Pan et al [ 9 ] give an overview of the role of hepatocyte nuclear factor 4α (HNF4α) in the pathogenesis of NAFLD. HNF4α has been shown to regulate bile acid, lipid, and glucose metabolism; and hepatic HNF4α expression is much lower in patients with NAFLD and mouse models of NASH.…”

“…Furthermore, there is evidence that hepatic HNF4α plays a key role in the initiation and progression of NAFLD and may represent a therapeutic target for NAFLD. [ 9 ]…”

“…Furthermore, there is evidence that hepatic HNF4a plays a key role in the initiation and progression of NAFLD and may represent a therapeutic target for NAFLD. [9] Huang et al [10] presented a systematic review regarding the role of retinol-binding protein 4 (RBP4) in the development of NAFLD and its potential therapeutic application. RBP4 induces hepatic de novo lipogenesis, impairs fatty acid oxidation, increases insulin resistance, and promotes hepatic inflammation.…”