Chylomicron-Derived Fatty Acid Spillover in Adipose Tissue: A Signature of Metabolic Health?

Abstract

Spillover of fatty acids (FAs) into the plasma nonesterified fatty acid (NEFA) pool, because of an inability of adipose tissue (AT) to accommodate sufficient fat uptake, has been suggested to contribute to obesity-related insulin resistance. Using specific labeling techniques, we compared the proportion of spillover-derived NEFA across a range of adiposity. Seventy-one healthy men and women were fed a mixed meal (40 g fat) containing [U13C]palmitate to assess the contribution of chylomicron-derived spillover FAs. To investigate subcutaneous abdominal-specific spillover, arteriovenous difference and stable-isotope methodologies were used in substudy (six men, six women). Chylomicron-derived FA spillover was higher in individuals with a BMI <25 kg/m2 (n = 18) compared with those with a BMI ≥25 kg/m2 (n = 53) (22.2 ± 1.6% vs 18.6 ± 0.7%, P = 0.02). Women had higher chylomicron-derived FA spillover than age- and BMI-matched men (21.9 ± 1.1% vs 15.0 ± 1.6%, P = 0.001). Assessing spillover across subcutaneous abdominal AT showed higher proportions in women than in men (28.5 ± 6.1% vs 9.9 ± 1.3%, P = 0.01). There is a considerable degree of spillover FA into the systemic NEFA pool in the postprandial state; this process is greater and more dynamic in lean individuals and women. Contrary to general perception, spillover of chylomicron-derived FA into systemic circulation is a physiologically normal feature most easily observed in people with a higher capacity for clearance of plasma triglycerides, but does not appear to be a pathway providing excess NEFA in obesity.