Gene expression was measured during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice (n = 185) were allotted to a 2 x 2 factorial experiment consisting of either nonobese (ICR-control) or obese (M16-selected) mice fed a 7% fat, purified diet containing either 1% linoleic acid (LA) or 1% t10c12-CLA. Body weight (BW) by day 14 was 12% lower in CLA- compared with 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 pools per tissue per day) from epididymal adipose (days 5 and 14) of the obese mice to analyze gene expression profiles using Agilent mouse oligo microarray slides representing > 20,000 genes. Numbers of genes differentially expressed by greater than or equal to twofold in epididymal adipose (days 5 and 14) were 29 and 125, respectively. It was concluded that, in adipose tissue, CLA increased expression of uncoupling proteins (1 and 2), carnitine palmitoyltransferase system, tumor necrosis factor-alpha (P < 0.05), and caspase-3 but decreased expression of peroxisome proliferator-activated receptor-gamma, glucose transporter-4, perilipin, caveolin-1, adiponectin, resistin, and Bcl-2 (P < 0.01). In conclusion, this experiment has revealed candidate genes that will be useful in elucidating mechanisms of adipose delipidation.