| Conjugated linoleic acids (CLA) are a group of positional and geometric isomers of linoleic acid. The two major isomers, cis-9,trans-11 (c9t11) and trans-10,cis-12 (t10c12) CLA, have been reported as having numerous biological effects including anti-carcinogenic, anti-atherogenic, immune modulating, and body fat reduction. The anti-obesity activity in many animal models is due specifically to t10c12 CLA, but its molecular mechanism has not been elucidated. This study was performed to investigate CLA's possible mechanism of anti-adipogenicity and its regulation of gene expression in adipose tissue.; First, we found that a t10c12 CLA containing diet did not make significant change in food intake, while it reduced leptin expression in adipose tissue, and this reduction was similar to that caused by treatment with thiazolidinedione (TZD), a peroxisome proliferator-activated receptor γ (PPARγ) activator. The results indicated that CLA action might occur through PPARγ pathway.; We observed that t10c12 CLA inhibited the preadipocyte differentiation process as well as TZD action in 3T3-L1 adipocytes. However, CLA did not interfere with TZD's anti-diabetic effect in vivo and TZD did not affect CLA's anti-obesity effect either. We concluded that CLA and TZD did not share a common signaling pathway, but the synergistic interaction between CLA and TZD indicated that CLA could be a useful adjunct to the treatment of diabetes with TZD-type pharmaceuticals.; Although t10c12 CLA induced insulin resistance in vivo, it did not affect insulin-stimulated glucose uptake and rather enhanced basal glucose uptake through induction of glucose transporter 1 protein expression. We also observed that the diet supplemented with t10c12 CLA, but not the c9t11 isomer, reduced glucose transporter 4 (GLUT4) protein levels in adipose tissue. This reduction was overcome with a diet change to c9t11 CLA diet, which indicated that suppression of GLUT4 was reversible.; In addition to the PPARγ pathway, affecting stearoly-CoA desaturase (SCD) has been suggested as a plausible mechanism of CLA's action. To prove this hypothesis, SCD1 wild-type and knock-out mice were used and t10c12 CLA was fed to both strains. T10c12 CLA reduced body fat mass and changed serum parameters in SCD1 knock out mice as in wild-type mice, which proved that the influence of t10c12 CLA on reducing body fat gain appeared to be independent of the SCD1 gene. |
