Abstract P220: Elevated De Novo Lipogenesis Fatty Acids and Lower Omega-6 Fatty Acids Are Associated With Markers of Insulin Resistance and Respond to Changes in Dietary Carbohydrate Intake in Overweight Individuals on Weight Loss Diets

Abstract

Background: High blood levels of certain fatty acids (FAs) in the de novo lipogenesis pathway (DNL; i.e., 16:0, cis-16:1n7) and low levels of omega-6 FAs (n-6 FA; i.e., 18:2n6) have been related to increased risk for type 2 diabetes. We hypothesized that individuals with insulin resistance (IR) would have higher DNL and lower n-6 FA plasma levels than insulin sensitive (IS) individuals, and that DNL FA levels would decrease on a low-carbohydrate (LC) diet and not change on a low-fat (LF) diet. Methods: Plasma FAs were measured as a % of total FA in subjects (n=61) with varying degrees of obesity and IR before and after 6 months of LF or LC weight loss diets. IR metrics were calculated pre- and post from oral glucose tolerance tests and fasting blood samples. FA medians (Interquartile Range), Spearman correlations (R) and Mann-Whitney test results are presented. Results: All differences shown are significant at P<0.05 unless reported as not significant (NS). Compared to the IS group, IR individuals had higher 16:0 (IR: 22.9% [22.2, 24.3] vs IS: 21.7% [20.2, 22.5]) and 16:1n7 (IR: 1.8% [1.4, 2.2] vs IS: 1.3% [1.1, 1.6]), and lower 18:2n6 (IR: 30.8% [27.8, 31.6] vs IS: 32.5% [30.0, 34.6]) levels at baseline. 16:0 and 16:1n7 were directly related to BMI (0.40, 0.28), fasting insulin (0.40, 0.33), HOMA-IR (0.40, 0.43), TG:HDL (0.38, NS) and indirectly to Matsuda Index (-0.35, -0.34). 18:2n6 was directly related to the Matsuda Index (0.35) and indirectly to HOMA-IR (-0.37) and TG:HDL (-0.45). Diet x IR status analyses were not significant, thus FA changes on LC and LF diets were compared. 16:1n7 decreased on the LC diet and did not change on the LF diet (LC: -0.5% [-0.7, -0.3] vs LF: -0.1% [-0.3, 0.2]). 18:2n6 levels increased on the LC diet and decreased on the LF diet (LC: 0.9% [-0.3, 2.7] vs LF: -0.5% [-2.4, 0.6]). Changes in dietary carbohydrate (% of calories) correlated with changes in 16:1n7 directly (0.38) and 18:2n6 indirectly (-0.37). Changes in 16:1n7 were directly related to changes in weight (0.55) and TG:HDL (0.65), and changes in 18:2n6 were indirectly related to TG:HDL changes (-0.51). Conclusions: Elevated plasma DNL FA and lower 18:2n6 were evident in IR vs. IS individuals, and individual markers of IR were related to FA levels accordingly. DNL and 18:2n-6 responded to changes in carbohydrate intake. FA patterns may be a useful tool to identify IR individuals and track carbohydrate consumption.