Increased lipid availability for three days reduces whole body glucose uptake, impairs muscle mitochondrial function and initiates opposing effects on PGC-1α promoter methylation in healthy subjects.

AIMS:FFA and FFA metabolites cause insulin resistance and impair beta cell function. The goal of our research was to examine whether elevation of plasma FFA impairs mitochondrial function and alters PGC-1α promoter methylation. METHODS:In this uncontrolled, change from baseline study design, insulin sensitivity and glucose-stimulated insulin secretion were measured in 9 normal glucose tolerant subjects before and after 3 day lipid infusion to elevate plasma FFA concentration. Vastus lateralis muscle biopsies were obtained and mitochondrial function, PGC-1α expression, and PGC-1α promoter methylation were quantitated. RESULTS:Increased plasma FFA (440±93 μmol/Lto 997±242 μM, p