The effect of enterolactone on liver lipid precursors of inflammation

Life Sci. 2019 Mar 15:221:341-347. doi: 10.1016/j.lfs.2019.02.044. Epub 2019 Feb 22.

Abstract

Aims: The aim of this study was to assess the effects of enterolactone (ENL) on lipid fractions fatty acids composition affecting hepatocyte inflammation development.

Main methods: The experiments were conducted in HepG2 cells incubated with ENL and/or palmitic acid (16 h). Intracellular contents of free fatty acids (FFA), di- (DAG) and tri- (TAG) acylglycerol as well as their fatty acids compositions were assessed by Gas-Liquid Chromatography. Moreover, the ω-6/ω-3 ratios in the above mentioned lipids fractions were estimated. The expression of proteins involved in eicosanoids and prostanoids production (COX-2, 15-LOX), inflammatory process (TNFα), as well as the proteins participating in the desaturation (SCD 1) and elongation (Elovl 3, Elovl 6) of fatty acids were evaluated by Western Blot.

Key findings: Enterolactone modified fatty acids composition in FFA, DAG and TAG fractions. In conjunction with lipid overload, it increased the content of ω-6 more than ω-3 PUFA. Moreover, it enhanced the expressions of Elovl 3, Elovl 6, COX-2 and TNFα, whereas it had no influence on SCD 1 and 15-LOX level.

Significance: Our study revealed that the supplementation with ENL affected intracellular hepatic composition of saturated as well as unsaturated fatty acids in each of the investigated lipid fractions. Based on the shift in the ω-6/ω-3 balance towards ω-6, as well as the increase in COX-2 and TNFα protein expressions, we may postulate a pro-inflammatory nature of the examined polyphenol. Moreover, our findings could prove to be useful in the future research in the topic of widespread diseases such as NASH.

Keywords: Enterolactone; Fatty acids; Hepatocytes; Inflammation; Nonalcoholic fatty liver disease.

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / metabolism
  • 4-Butyrolactone / pharmacology
  • Eicosanoids
  • Fatty Acids
  • Fatty Acids, Nonesterified / analysis
  • Fatty Acids, Nonesterified / metabolism*
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • Hep G2 Cells / drug effects
  • Hepatocytes
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Lignans / metabolism*
  • Lignans / pharmacology
  • Lipid Metabolism
  • Lipids
  • Liver / drug effects
  • Palmitic Acid / pharmacology
  • Prostaglandins
  • Triglycerides / analysis

Substances

  • Eicosanoids
  • Fatty Acids
  • Fatty Acids, Nonesterified
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • Lignans
  • Lipids
  • Prostaglandins
  • Triglycerides
  • Palmitic Acid
  • 4-Butyrolactone
  • 2,3-bis(3'-hydroxybenzyl)butyrolactone