314-OR: The Effect of Inhibition of Fatty Acid Spillover from Adipose Tissues on Organ-Specific Distribution of Dietary Fatty Acids

Excessive exposure of lean tissues to fatty acids leads to insulin resistance. Proper dietary fatty acids (DFA) storage in white adipose tissue (WAT) is thought to prevent lean tissue lipotoxicity. We showed that WAT storage of DFA was impaired in IGT (impaired glucose tolerance) and was associated with greater cardiac DFA uptake and subclinical left-ventricular dysfunction. Whether WAT DFA storage directly impacts cardiac DFA uptake in IGT subjects is not known. We aimed at investigating how inhibition of intracellular lipolysis affected WAT DFA storage, spillover, and cardiac DFA uptake. We recruited 23 participants: 12 IGT, 5 women/7 men, aged (mean ± sem) 64±2.5, BMI= 34.9±3.1 kg/m² and 11 NGT, 7 women/4 men, aged 62±2, BMI= 30.4±1.6 kg/m². Cardiac DFA uptake and whole-body organ-specific DFA partitioning were assessed using PET/CT method with oral administration of ¹⁸FTHA. NEFA appearance and WAT DFA spillover were measured using stable isotope tracer methods. Nicotinic acid (NA) was used to inhibit WAT DFA spillover. In both groups, NA decreased AUC DFA spillover rate (-31%±19, p=0.014) and AUC NEFA appearance rate (-28%±10, p=0.0002). In NGT group, NA decreased muscle and liver DFA distribution by 30%±8 (p=0.007) and 25%±8 (p=0.024), respectively, and increased WAT DFA distribution by 48%±8 (p=0.001). The same trend was observed in IGT group, but with blunted differences in WAT DFA storage vs. NGT (p=0.73). NA-induced increase in visceral WAT DFA distribution was correlated negatively with change in AUC. Nonesterified fatty acids (NEFA) appearance rate (ρ=-0.58, p=0.004). In both groups, NA did not significantly affect cardiac DFA distribution. In both groups, we estimated that DFA spillover may account for 31%±23 of DFA reaching lean organs over a 6-hour period after meals. Inhibition of WAT DFA spillover enhances DFA WAT storage and reduces liver and skeletal muscle, but not cardiac DFA partitioning.