We investigated whether free fatty acids (FFA) mediate the association between adiposity and insulin resistance in the Hispanic-American families of the Insulin Resistance Atherosclerosis Family Study.

In 815 Hispanic individuals in the Insulin Resistance Atherosclerosis Family Study, we tested for association between the following: 1) levels of adiposity [body mass index (BMI), visceral and sc adipose tissue area (VAT and SAT)] and circulating levels of FFA; 2) levels of circulating FFA and insulin sensitivity (S_I); and 3) levels of adiposity and S_I, additionally testing to see whether levels of FFA mediated or modified the relationship between adiposity and S_I.

After adjusting for age, sex, clinic site, and admixture, increasing levels of BMI, VAT, and SAT were weakly associated with increasing levels of circulating FFA (BMI: P = 0.024; VAT: P = 2.33 × 10⁻³; SAT: P = 0.018; percent variation explained: ∼1.00%). Increasing levels of circulating FFA were associated with decreasing S_I (P = 8.10 × 10⁻¹¹). Increasing BMI, VAT, and SAT were also associated with decreasing S_I (BMI: P = 4.98 × 10⁻⁷¹; VAT: P = 1.48 × 10⁻⁶⁴; SAT: P = 4.21 × 10⁻⁶²), but this relationship was not significantly mediated by FFA. VAT, but not BMI or SAT, interacts with levels of FFA to influence S_I (P = 0.021).

Although levels of circulating FFA are associated both with increasing adiposity and decreasing S_I, they do not appear to mediate the association between levels of adiposity and S_I in this large cohort of Hispanic-Americans. These results may indicate that FFA contribute to insulin resistance independent of adiposity.