Isomer-specific antidiabetic properties of conjugated linoleic acid - Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression

Conjugated linoleic acid (CLA) isomers have a number of beneficial health e ffects, as shown in biomedical studies with animal models. Previously, we r eported that a mixture of CLA isomers improved glucose tolerance in ZDF rat s and activated peroxisome proliferator-activated receptor (PPAR)-gamma res ponse elements in vitro. Here, our aim was to elucidate the effect(s) of sp ecific CLA isomers on whole-body glucose tolerance, insulin action in skele tal muscle, and expression of genes important in glucose and Lipid metaboli sm. ZDF rats were fed either a control diet (CON), one of two CLA supplemen ted diets (1.5% CLA) containing differing isoforms of CLA (47% c9,t11; 47.9 % c10,t12, 50:50; or 91% c9,t11, c9,t11 isomers), or were pair-fed CON diet to match the intake of 50:50. The 50:50 diet reduced adiposity and improve d glucose tolerance compared with all other ZDF treatments. Insulin-stimula ted glucose transport and glycogen synthase activity in skeletal muscle wer e improved with 50:50 compared with all other treatments. Neither phosphati dlyinositol 3-kinase activity nor Akt activity in muscle was affected by tr eatment. Uncoupling protein 2 in muscle and adipose tissue was upregulated by c9,t11 and 50:50 compared with ZDF controls. PPAR-gamma mRNA was downreg ulated in liver of c9,t11 and pair-fed ZDF rats. Thus, the improved glucose tolerance in 50:50 rats is attributable to, at least in part, improved ins ulin action in muscle, and CLA effects cannot be explained simply by reduce d food intake.