Conjugated Linoleic Acid Decreases Insulin Sensitivity and Increases Skeletal Muscle Ceramides in Overweight, Sedentary Humans

Abstract

BACKGROUND. The effect of conjugated linoleic acid (CLA) on insulin sensitivity (IS) in humans is controversial with some studies demonstrating an improvement and others a worsening of IS. In Zucker diabetic fatty rats, CLA improves IS and this is correlated with a reduction in intramuscular triglycerides (IMTG). Elelvated IMTG is associated with the development of insulin resistance; however it is likely the more reactive lipid species such as diglycerides (DG) and ceramides that cause insulin resistance by interfering with insulin signaling in skeletal muscle. To date, no research has attempted to measure skeletal muscle ceramide and DG content following CLA treatment. The PURPOSE of this research was to determine the effects of CLA on IS and skeletal muscle lipid content in overweight, non-diabetic humans. It is hypothesized that CLA will improve IS with an associated reduction in skeletal muscle IMTG, DG and ceramide content in skeletal muscle. METHODS: Nine overweight, non-diabetic, sedentary humans (BMI 29.6 ± 0.6 kg/m2, age 31.2 ± 3.7 yrs) were supplemented with 4 g of mixed isomer CLA/dfor 12 weeks. Subjects underwent oral glucose tolerance tests and resting skeletal muscle biopsies prior to and following supplementation. Total and individual species of skeletal muscle IMTG, DG and ceramides were measured prior to and following CLA treatment. Blood samples were assessed for glucose and insulin in response to the oral glucose tolerance test. RESULTS: Glucose and insulin area under the curves were significantly increased following CLA supplementation with a resultant 20 % decrease in insulin sensitivity (p <0.05). Total (prevs post 403.1 ±34.4 vs. 660.3 ± 144.0) and polyunsaturated (81.4 ± 9.0 vs. 148.3 ± 32.1) ceramide content was significantly increased following CLA supplementation (p < 0.05). There was a trend towards an increase in total saturated and monounsaturated fatty acid species (p <0.06). Total DG and IMTG were not changed following treatment. CONCLUSION. This research demonstrates that CLA supplementation decreases insulin sensitivity in overweight, sedentary individuals. This reduction in insulin sensitivity may have been the result of elevated skeletal muscle ceramide content interfering with enzymes involved with the insulin signaling pathway.