Insulin Resistance, Inflammation, and Serum Fatty Acid Composition

Abstract

OBJECTIVE—Fatty acids (FAs) have been involved in the development of chronic inflammatory conditions such as insulin resistance and obesity. However, the relation among insulin resistance, obesity, inflammatory activity (circulating interleukin [IL]-6) and dietary FAs has been scarcely studied in otherwise healthy subjects. RESEARCH DESIGN AND METHODS—We aimed to study these interactions in 123 overweight (BMI 26.9 ± 2.4 kg/m2 [means ± SD]) subjects and 109 lean (BMI 21.7 ± 1.7 kg/m2, P < 0.000001) subjects. IL-6 was measured by immunoassay and FA by gas liquid cromatography. RESULTS—The percentage of saturated FAs (r = 0.30, P = 0.01) and ω-6 FAs (r = −0.32, P = 0.001) were significantly associated with circulating IL-6, whereas the percentage of ω-3 FAs correlated negatively with C-reactive protein in overweight subjects (P = 0.04). Saturated-to-ω-3 and saturated-to-ω-6 FA ratios were significantly and positively associated with C-reactive protein (P < 0.0001) and IL-6 (P < 0.001), respectively. In contrast, none of these associations reached statistical significance in lean subjects. Those subjects in the most insulin-sensitive quintile (homeostasis model assessment value) showed a significantly higher percentage of linoleic acid (C18:2 ϖ6) (P = 0.03) and a significantly lower level of araquidic (C20:0) (P = 0.04), behenic (C22:0) (P = 0.009), lignoceric (C24:0) (P = 0.02), and nervonic (C24:1 ϖ9) (P = 0.001) FAs than the remaining subjects. In parallel, the most insulin-sensitive subjects showed significantly decreased C-reactive protein (P = 0.03). Serum C-reactive protein was significantly associated with percent linoleic acid and eicosapentaenoic acid in nonsmoking men (P = 0.03 and P = 0.04, respectively) and with docosahexaenoic acid in nonsmoking women (r = −0.46, P < 0.0001). We constructed a multivariant regression analysis to predict circulating IL-6. Age, BMI, waist-to-hip ratio (WHR), smoking status, and the relation of saturated to ω-6 or saturated to ω-3 FAs were considered as independent variables separately in men and women. In overweight men, the ratio of saturated to ω-3 FAs (P = 0.01), but not age, sex, BMI, WHR, or smoking status, independently contributed to 17% of IL-6 variance. In lean men, smoking status (P = 0.02), but not the remaining variables, contributed to 8% of IL-6 variance. CONCLUSIONS—Dietary FAs (as inferred from plasma FA concentration) seem to be linked to inflammatory activity in overweight subjects and in subjects with insulin resistance. Being overweight modulates the relation of FAs to inflammatory markers.