Diverse inhibition of forkhead box O1 activity by linoleic acid isomers - potential role in lipid metabolism in HepG2 cells and livers of C57BL/6J mice

J Physiol Pharmacol. 2019 Jun;70(3). doi: 10.26402/jpp.2019.3.05. Epub 2019 Sep 18.

Abstract

Conjugated dienes of linoleic acid (CLA) are constitutional and geometric isomers of linoleic acid that are commonly used as dietary supplements during body mass reduction. Their role in the reduction of lipid deposits in liver tissue is not unequivocal. CLA contain an equimolar mixture of two isomers of linoleic acid: trans-10,cis-12 CLA and cis-9,trans-11. Only one isomer - trans-10,cis-12 CLA exhibits fat-reducing properties, cis-9,trans-11 CLA does not. The main goal of this study was to determine if CLA isomers affect the activation of forkhead box O1 (FoxO1) in liver cells and tissue. FoxO1 is a protein that plays a crucial role in regulation of lipid and carbohydrates metabolism. In vitro and in vivo models of our study were HepG2 cells and C57BL/6J mice. Methods used in the study were qPCR - quantification of FoxO1 gene expression, Western blot - posttranslational phosphorylation of FoxO1, Oil Red O (ORO) - lipid staining and ELISA - quantification of apoB100. In both models trans-10,cis-12 CLA diminished FoxO1 gene expression: decrease by 44.1 ± 20.9% SD in the cells and 65.4 ± 29.8% SD in mice. The lowest accumulation of lipids (drop of 37.2 ± 1.7% SD) and the highest increase of apoB100 protein (74 ± 12.8% SD) were detected in the medium of cells cultured with trans-10,cis-12 CLA. Both isomers of linoleic acid have different effects on lipid metabolism. Isomer c9,t11 CLA accelerates lipogenesis, whereas isomer t10,c12 CLA activates secretion of lipids in HepG2 cells. In contrast to the in vitro study, unfortunately this pro-health property of t10,c12 CLA was not confirmed in the in vivo model. This casts a shadow on CLA dietary supplements that are commonly used among people with type 2 diabetes, NAFLD (non-alcoholic liver disease) or a metabolic syndrome in order to lose weight.

MeSH terms

  • Animals
  • Body Weight / drug effects
  • Cell Line, Tumor
  • Dietary Supplements
  • Female
  • Forkhead Box Protein O1 / antagonists & inhibitors*
  • Gene Expression / drug effects
  • Hep G2 Cells
  • Humans
  • Linoleic Acids, Conjugated / pharmacology*
  • Lipid Metabolism / drug effects*
  • Lipids / physiology
  • Liver / drug effects*
  • Liver / metabolism
  • Mice
  • Mice, Inbred C57BL

Substances

  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Linoleic Acids, Conjugated
  • Lipids