Functional Genomic Characterization of the Anti-Adipogenic Effects of trans 10, cis 12-Conjugated Linoleic Acid (t10c12-CLA) in a Polygenic Obese Line of Mice
We analyzed gene expression during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice (N=185) were allotted to a 2x2 factorial experiment consisting of a non-obese (ICR-control) and an obese (M16-selected) line of mice fed a 7% fat, purified diet containing either 1% linoleic acid (LA) or 1% t10c12-CLA. Body weight (BW) gain by day 14 was 12% lower in CLA compared to LA fed mice (P<0.0001). By day 14, t10c12-CLA reduced weights of epididymal, mesenteric and brown adipose tissues as a percentage of BW in both lines by 30, 27 and 58%, respectively, and increased liver weight/BW by 34% (P<0.0001). Total RNA was isolated and pooled (4-5 mice per composite) from epididymal adipose (day 5 & 14) and liver (day 14) of the obese mice to analyze gene expression profiles using Agilent mouse oligo microarray slides (4 per tissue?day) representing >20,000 genes. Numbers of genes differentially expressed by ? two fold in epididymal adipose (day 5 & 14) and liver (day 14) were 29, 125, and 80, respectively. Of particular interest in adipose, CLA putatively increased expression of the uncoupling proteins (1 and 2), carnitine palmitoyltransferase (L and M), and carnitine translocase, but decreased expression of PPAR-gamma, GLUT-4, perilipin, caveolin-1, adiponectin and resistin (P<0.01). In conclusion, this experiment has revealed candidate genes that will be useful in elucidating mechanisms underlying the potent anti-adipogenic effects of t10c12-CLA.
Advisor:Eugene J Eisen; David S Lalush; Joseph P Cassady; Jack Odle
School:North Carolina State University
School Location:USA - North Carolina
Source Type:Master's Thesis
Date of Publication:07/29/2004