PPARα protects against trans-fatty-acid-containing diet-induced steatohepatitis

J Nutr Biochem. 2017 Jan:39:77-85. doi: 10.1016/j.jnutbio.2016.09.015. Epub 2016 Oct 11.


Consumption of trans-fatty acids (TFA), unsaturated fatty acids (FA) containing trans double bonds, is a risk factor for metabolic syndrome and steatohepatitis. Peroxisome proliferator-activated receptor α (PPARα) is a master regulator of hepatic lipid homeostasis. To examine the contribution of PPARα to changes in liver phenotypes induced by TFA, two diets were used: a purified control diet and an isocaloric diet in which most of the soybean oil, a major source of FA in the diet, was replaced with TFA-rich shortening. The diets were fed to wild-type and Ppara-null mice for 2 months. Ppara-null mice fed a TFA-containing diet showed more severe hepatic steatosis and liver damage compared with similarly treated wild-type mice, as revealed by increased hepatic triglyceride (TG) contents and serum alanine aminotransferase activities. While the TFA-rich diet increased the hepatic expression of enzymes involved in de novo FA synthesis and decreased TG-hydrolyzing enzymes in both genotypes, the expression of FA-catabolizing enzymes was decreased in Ppara-null mice, resulting in more severe hepatosteatosis. Additionally, the expression levels of key contributors to inflammation, such as osteopontin, were increased, and nuclear factor-kappa B was activated in TFA-containing diet-fed Ppara-null mice. Enhanced inflammatory signaling in these mice was presumably mediated by toll-like receptor 2, with no accompanying inflammasome activation. Collectively, these results suggest a protective role for PPARα in the pathological changes in the liver following TFA consumption. PPARα might prevent TFA-containing diet-induced steatohepatitis.

Keywords: Inflammasome; Nuclear factor-kappa B; Osteopontin; PPARα; Toll-like receptor; trans-Fatty acid.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Diet
  • Dietary Fats / administration & dosage
  • Dietary Fats / adverse effects*
  • Fatty Liver / etiology
  • Fatty Liver / therapy*
  • Lipogenesis
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice
  • PPAR alpha / metabolism*
  • Risk Factors
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism
  • Trans Fatty Acids / administration & dosage
  • Trans Fatty Acids / adverse effects*
  • Triglycerides / blood


  • Dietary Fats
  • PPAR alpha
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Trans Fatty Acids
  • Triglycerides
  • Alanine Transaminase