Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion

The effect of hyperglycemia (~8 mmol/l) on splanchnic fatty acid oxidation and triacylglycerol (TG) secretion rates was investigated in five healthy men. U-¹³C-labeled fatty acids were infused to estimate fatty acid kinetics and oxidation across the splanchnic region, and in vivo labeled very low density lipoprotein (VLDL)-TG was infused to estimate TG secretion rate. Plasma fatty acid carbon enrichment and concentration were maintained constant by infusion of lipids and heparin in the hyperglycemia experiments. Fatty acid uptake by the splanchnic region was 1.4 ± 0.2 and 2.2 ± 0.9 μmol · kg^-1 · min^-1 in the basal and clamp experiments, respectively, whereas fatty acid oxidation decreased from 0.4 ± 0.04 to 0.2 ± 0.05 μmol · kg^-1 · min^-1 (P < 0.05). Hepatic TG secretion increased from 0.35 ± 0.07 μmol · kg^-1 · min^-1 in the basal state to 0.53 ± 0.11 μmol · kg^-1 · min^-1 after 15 h of hyperglycemia (P < 0.05). Similarly, plasma VLDL-TG concentration increased from 0.28 ± 0.06 to 0.43 ± 0.05 mmol/l during the clamp (P < 0.05). In summary, hyperglycemia attenuates fatty acid oxidation in the splanchnic region in human volunteers, even when fatty acid availability is constant. This adaptation results in a significant increase in the VLDL-TG secretion rate and concentration in plasma.