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

INTRODUCTION: 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. AIM: 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. METHODS: Basal acetate Ra was measured following an overnight fast in lean (BMI: 21.3 ± 1.1 Kg/m2) and obese (30.2 ± 0.9 Kg/m2, P = 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. RESULTS: Basal acetate Ra was 30% higher in the lean compared to the obese subjects (257 ± 27 vs. 173 ± 18 µmol/min; P = 0.025). Basal plasma insulin concentrations were 4-fold higher in the obese than the lean subjects (P = 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 (P = 0.015). During the hyperglycemic clamp, plasma ghrelin decreased by 42% in the lean group (P < 0.022 vs. basal) and did not change in the obese group. CONCLUSION: 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.