Chrysin ameliorates hepatic steatosis induced by a diet deficient in methionine and choline by inducing the secretion of hepatocyte nuclear factor 4α-dependent very low-density lipoprotein

J Biochem Mol Toxicol. 2020 Jul;34(7):e22497. doi: 10.1002/jbt.22497. Epub 2020 Mar 27.

Abstract

We investigated the effects of chrysin (CHR) on nonalcoholic fatty liver disease (NAFLD) in mice. The NAFLD mouse model was established using a diet deficient in methionine and choline (MCD). CHR was shown to attenuate MCD-induced hepatic fat accumulation, increase very low-density lipoprotein (VLDL) secretion, and decrease hepatic oxidative stress in NAFLD mice. Inhibition of oxidative stress or direct suppression of protein kinase C (PKC) by CHR significantly reduced PKC activity in the liver, leading to a decrease in inhibitory phosphorylation of hepatocyte nuclear factor 4α (HNF4α). The resulting activation of HNF4α led to induced transcription of apolipoprotein B and VLDL secretion. Together, these results show that CHR effectively ameliorates MCD-induced fatty liver in NAFLD mice by targeting the hepatic oxidative stress/PKC/HNF4α signaling pathway.

Keywords: ApoB; HNF4α; chrysin; methionine and choline deficient.

MeSH terms

  • Animals
  • Choline Deficiency / complications*
  • Diet / adverse effects*
  • Diet / methods
  • Disease Models, Animal
  • Flavonoids / administration & dosage*
  • Hep G2 Cells
  • Hepatocyte Nuclear Factor 4 / metabolism*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Lipoproteins, VLDL / metabolism*
  • Male
  • Methionine / deficiency*
  • Mice
  • Mice, Inbred C57BL
  • Non-alcoholic Fatty Liver Disease / drug therapy*
  • Non-alcoholic Fatty Liver Disease / etiology*
  • Oxidative Stress / drug effects
  • Protein Kinase C / metabolism
  • Secretory Pathway / drug effects*
  • Signal Transduction / drug effects
  • Treatment Outcome

Substances

  • Flavonoids
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • Hnf4a protein, mouse
  • Lipoproteins, VLDL
  • chrysin
  • Methionine
  • Protein Kinase C