| Conjugated linoleic acid (CLA) refers to a mixture of positional and geometric isomers of linoleic acid with conjugated double bonds. cis-9, trans-11 and trans-10, cis-12 CLA are the two major isomers in chemically synthesized CLA. In this dissertation, the mechanisms whereby CLA caused a significant reduction of body fat accumulation were investigated. Data obtained from feeding 0.5% CLA for 3–4 days indicate that in mice CLA-induced inhibition of heparinreleasable lipoprotein lipase activity and glucose metabolism may be the most important early steps leading to subsequent body fat reduction. When mice were fed 0.5% CLA for a longer time (2–6 weeks), the control group exhibited an increase in adipocyte size and number. On the other hand, in the CLA group adipocyte size was decreased while the adipocyte number at week 2 and week 6 was not significantly different from the baseline adipocyte number (week 0). DNA fragmentation assay showed CLA induced apoptosis in adipocytes and preadipocytes at week 2 and week 6, indicating that some degree of proliferation and differentiation of preadipocytes to offset apoptosis occurred in the CLA-fed mice. The effect of CLA on glucose uptake was further investigated in 3T3-L1 cells. trans-10, cis-12 CLA decreased insulin stimulated glucose uptake and GLUT4 content in 3T3-L1 cells, while cis-9, trans-11 CLA restored insulin stimulated glucose uptake in trans-10, cis-12 CLA-treated cells. cis -9, trans-11 and trans-10, cis-12 CLA treatment produced different fatty acid profiles in 3T3-L1 cells. In a 48 hr time-course study, the concentration of saturated fatty acids in trans-10, cis-12 CLA-treated 3T3-L1 cells was always higher and the concentration of mono-unsaturated fatty acid was always lower than those in cis-9, trans-11 CLA treated cells. These changes and their possible roles in CLA's biological effects are worth further investigation. |
