Functional genomic characterization of delipidation elicited by trans-10, cis-12-conjugated linoleic acid (t10c12-CLA) in a polygenic obese line of mice. Physiol Genomics 21: 351-361, 2005; doi: 10.1152/physiolgenomics.00244.2004.-Gene expression was measured during t10c12-CLA-induced body fat reduction in a polygenic obese line of mice. Adult mice (n ϭ 185) were allotted to a 2 ϫ 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 Ͻ 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 Ͻ 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 Ͼ20,000 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-␣ (P Ͻ 0.05), and caspase-3 but decreased expression of peroxisome proliferator-activated receptor-␥, glucose transporter-4, perilipin, caveolin-1, adiponectin, resistin, and Bcl-2 (P Ͻ 0.01). In conclusion, this experiment has revealed candidate genes that will be useful in elucidating mechanisms of adipose delipidation. apoptosis; cell biology; gene expression; lipid metabolism; obesity OVER THE PAST 20 YR, the incidence of obesity has reached epidemic proportions. According to the 1999-2000 National Health and Nutrition Examination Survey, ϳ64% of United States adults Ն20 yr old are overweight or obese (http:// www.cdc.gov/nchs/products/pubs/pubd/hestats/obese/obse99. htm) (28). In 2003, Sturm (53) reported that extreme obesity [body mass index (BMI) Ն40] quadrupled between 1986 and 2000 from 1 in 200 adults to 1 in 50. Additionally, within the same time period, there was an increase by a factor of five of Americans with a BMI Ն50, from 1 in 2,000 to 1 in 400 (53). Internationally, the World Health Organization reported that from 1995 to 2000, the number of obese adults worldwide increased from 200 million to over 300 million adults (http://www.who.int/nut/obs.htm). In 2003, $75 billion (US dollars) was spent on medical treatment ascribed to obesity, one-half of which was paid for by Medicare and Medicaid (23).The rapid increase in the prevalence of obesity has attracted much attention to the delipidative effects of conjugated linoleic acid (CLA). Found naturally in ruminant products (such as beef and cheese), the CLA family consists of several conjugated and stereoisomeric variations of linoleic acid (cis, cis-⌬ 9,12 -octadecad...