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

Received 9 December 2008; received in revised form 3 June 2009; accepted 23 June 2009. published online 05 October 2009.
Corrected Proof

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

Abbreviations: acox1, acetyl CoA oxidase 1, agpat2, 1-acylglycerol-3-phosphate O-acyltransferase 2, bcl6, B-cell leukemia/lymphoma 6, cAMP, cyclic adenosine monophosphate, CLA, conjugated linoleic acid, cyp1a1, cytochrome P450, family 1, subfamily a, polypeptide 1, cyp27a1, cytochrome P450, family 27, subfamily a, polypeptide 1, dgat2, diacylglycerol O-acyltransferase 2, egfr, epidermal growth factor receptor, FDR, false discovery rate, fasn, fatty acid synthase, HNF-4α, hepatocyte nuclear factor 4α transcription factor, igfbp2, insulin-like growth factor binding protein 2, LA, linoleic acid, me, malic enzyme, NF-κB, nuclear factor κB, pdcd8, programmed cell death 8, PKA, protein kinase A, ppargc1, peroxisome proliferative activated receptor, gamma, coactivator 1 alpha, SCD1, stearoyl CoA desaturase 1, slc10a1, solute carrier family 10 (sodium/bile acid cotransporter family), member 1, socs6, suppressor of cytokine signaling 6, srebp2, sterol regulatory element binding factor 2, stat, signal transducer and activator of transcription, Tie2, endothelial cell receptor tyrosine kinase, tspyl4, testis-specific Y-like 4.

Keywords: Gene expression, Mice, Liver, Conjugated linoleic acid, Obesity, Hepatic steatosis, Fatty liver

a Department of Animal Science, North Carolina State University, Raleigh, NC, USA

b Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

c NIEHS Microarray Group, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA

Corresponding author. Department of Animal Science, NC State University, Raleigh, NC 27695, USA. Tel.: +1 919 515 4050; fax: +1 919 515 6884.

☆ This work was funded in part by the North Carolina Agricultural Research Service and the NIH-NIEHS Intramural Research Program.

PII: S0955-2863(09)00137-5

doi:10.1016/j.jnutbio.2009.06.013