Trans-10, cis-12-conjugated linoleic acid alters hepatic gene expression in a polygenic obese line of mice displaying hepatic lipidosis

J Nutr Biochem. 2010 Sep;21(9):848-55. doi: 10.1016/j.jnutbio.2009.06.013. Epub 2009 Oct 3.

Abstract

The trans-10, cis-12 isomer of conjugated linoleic acid (CLA) causes a rapid reduction of body and adipose mass in mice. In addition to changes in adipose tissue, numerous studies have reported alterations in hepatic lipid metabolism. Livers of CLA-fed mice gain mass, partly due to lipid accumulation; however, the precise molecular mechanisms are unknown. To elucidate these mechanisms, we examined fatty acid composition and gene expression profiles of livers from a polygenic obese line of mice fed 1% trans-10, cis-12-CLA for 14 days. Analysis of gene expression data led to the identification of 1393 genes differentially expressed in the liver of CLA-fed male mice at a nominal P value of .01, and 775 were considered significant using a false discovery rate (FDR) threshold of .05. While surprisingly few genes in lipid metabolism were impacted, pathway analysis found that protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) pathways signaling pathways were affected by CLA treatment and 98 of the 775 genes were found to be regulated by hepatocyte nuclear factor 4alpha, a transcription factor important in controlling liver metabolic status.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fatty Liver / genetics
  • Fatty Liver / metabolism*
  • Gene Expression Profiling
  • Hepatocyte Nuclear Factor 4 / genetics
  • Linoleic Acids, Conjugated / pharmacology*
  • Liver / metabolism*
  • Male
  • Mice
  • Obesity / genetics
  • Obesity / metabolism*

Substances

  • Hepatocyte Nuclear Factor 4
  • Linoleic Acids, Conjugated
  • trans-10,cis-12-conjugated linoleic acid