Trans-10, cis-12-conjugated linoleic acid alters hepatic gene expression in a polygenic obese line of mice displaying hepatic lipidosis.
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.
Department of Animal Science, North Carolina State University, Raleigh, NC 27695, USA.
Melissa S
MS
Ashwell
Ryan P
RP
Ceddia
Ralph L
RL
House
Joseph P
JP
Cassady
Eugene J
EJ
Eisen
Thomas E
TE
Eling
Jennifer B
JB
Collins
Sherry F
SF
Grissom
Jack
J
Odle
D000818:Animals; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics; D044243:Linoleic Acids, Conjugated / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D009765:Obesity / Q000235:genetics / Q000378:metabolism*
D051557:Hepatocyte Nuclear Factor 4; D044243:Linoleic Acids, Conjugated; C496197:trans-10,cis-12-conjugated linoleic acid