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

• Published in: The Journal of nutritional biochemistry 2010-09, Vol.21 (9), p.848-855
• Main Authors: Ashwell, Melissa S., Ceddia, Ryan P., House, Ralph L., Cassady, Joseph P., Eisen, Eugene J., Eling, Thomas E., Collins, Jennifer B., Grissom, Sherry F., Odle, Jack
• Format: Article
• Language: English
• Subjects: Adipose tissue; Animals; Biological and medical sciences; Conjugated linoleic acid; Fatty liver; Fatty Liver - genetics; Fatty Liver - metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Hepatic steatosis; Hepatocyte Nuclear Factor 4 - genetics; Linoleic Acids, Conjugated - pharmacology; Liver; Liver - metabolism; Male; Mice; Obesity; Obesity - genetics; Obesity - metabolism; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2009.06.013

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 4α, a transcription factor important in controlling liver metabolic status.