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Context and Objective: Spillover of fatty acids (FAs) into the plasma non-esterified fatty acid (NEFA) pool, due to an inability of adipose tissue to accommodate sufficient fat uptake, has been suggested to be a contributing factor to insulin resistance in obesity. Using specific labelling techniques, we compared the proportion of spillover-derived NEFA across a range of adiposity. Participants and Methods: Seventy-one healthy men and women (22-64 years; BMI 20-35 kg/m2) were fed a mixed meal (40g fat) containing [U13C]palmitate to assess the contribution of chylomicron-derived spillover FAs. To investigate subcutaneous abdominal-specific spillover, arterio-venous difference and stable-isotope methodologies were used in sub-study (6 men, 6 women). Results: Chylomicron-derived FA spillover was significantly higher in individuals with a BMI <25kg/m2 (n=18) compared to those with a BMI ≥25kg/m2 (n=53) (22.2±1.6% vs 18.6±0.7%, P=0.02). Women had significantly 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 adipose tissue showed significantly higher proportions in women than in men (28.5±6.1% vs. 9.9±1.3%, P=0.01). Conclusion: These data demonstrate that there is a considerable degree of spillover FAs 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 triglyceride but does not appear to be a pathway providing excess NEFA in people with obesity.

Original publication




Journal article


J Clin Endocrinol Metab

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