The effects of increased acetate turnover on glucose-induced insulin secretion in lean and obese humans

Increased endogenous acetate production (Ra) in rodents has been shown to activate the parasympathetic nervous system and thereby promote increased glucose-stimulated insulin secretion (GSIS), increased ghrelin secretion, hyperphagia and obesity. To examine whether rates of acetate turnover are different in lean versus obese humans and whether increased acetate turnover promotes increased GSIS and increased ghrelin secretion in humans. Basal acetate Ra was measured following an overnight fast in lean (BMI: 21.3 ± 1.1 Kg/m ) and obese (30.2 ± 0.9 Kg/m , = 0.00001) individuals. The subjects underwent two hyperglycemic (10 mmol/L) clamp studies to measure GSIS during a basal acetate infusion and during a high-dose acetate infusion increasing plasma acetate concentrations ∼5-fold. Basal acetate Ra was 30% higher in the lean compared to the obese subjects (257 ± 27 vs. 173 ± 18 μmol/min; = 0.025). Basal plasma insulin concentrations were 4-fold higher in the obese than the lean subjects ( = 0.008) and increased 5-fold during hyperglycemia in both groups, independent of changes in plasma acetate concentrations. Fasting plasma ghrelin concentrations were 35% lower in the obese compared to the lean subjects ( = 0.015). During the hyperglycemic clamp, plasma ghrelin decreased by 42% in the lean group ( < 0.022 vs. basal) and did not change in the obese group. Rates of endogenous acetate turnover are ∼30% higher in the lean subjects compared to the obese subjects, and increasing plasma acetate turnover does not promote increased GSIS or ghrelin secretion in either group.