Increased postprandial nonesterified fatty acid efflux from adipose tissue in prediabetes is offset by enhanced dietary fatty acid adipose trapping.

The mechanism of increased postprandial nonesterified fatty acid (NEFA) appearance in the circulation in impaired glucose tolerance (IGT) is due to increased adipose tissue lipolysis but could also be contributed to by reduced adipose tissue (AT) dietary fatty acid (DFA) trapping and increased "spillover" into the circulation. Thirty-one subjects with IGT (14 women, 17 men) and 29 with normal glucose tolerance (NGT, 15 women, 14 men) underwent a meal test with oral and intravenous palmitate tracers and the oral [F]-fluoro-thia-heptadecanoic acid positron emission tomography method. Postprandial palmitate appearance (Ra) was higher in IGT versus NGT ( < 0.001), driven exclusively by Ra from obesity-associated increase in intracellular lipolysis ( = 0.01), as Ra from DFA spillover was not different between the groups ( = 0.19) and visceral AT DFA trapping was even higher in IGT versus NGT ( = 0.02). Plasma glycerol appearance was lower in IGT ( = 0.01), driven down by insulin resistance and increased insulin secretion. Thus, we found higher AT DFA trapping, limiting spillover to lean organs and in part offsetting the increase in Ra from intracellular lipolysis. Whether similar findings occur in frank diabetes, a condition also characterized by insulin resistance but relative insulin deficiency, requires further investigation (Clinicaltrials.gov: NCT04088344, NCT02808182). We found higher adipose tissue dietary fatty acid trapping, limiting spillover to lean organs, that in part offsets the increase in appearance rate of palmitate from intracellular lipolysis in prediabetes. These results point to the adaptive nature of adipose tissue trapping and dietary fatty acid spillover as a protective mechanism against excess obesity-related palmitate appearance rate from intracellular adipose tissue lipolysis.