CLINICAL STUDY Free fatty acids decrease circulating ghrelin concentrations in humans

Objective: Concentrations of the orexigenic peptide ghrelin is affected by a number of hormones, which also affect circulating levels of free fatty acids (FFAs). The present study was therefore designed to determine the direct effect of FFAs on circulating ghrelin. Design: Eight lean, healthy men were examined for 8 h on four occasions using variable infusion rates (0, 3, 6 and 12ml/kg per min) of intralipid to create different plasma FFA concentrations. Constant levels of insulin and GH were obtained by administration of acipimox (250 mg) and somatostatin (300mg/h). At the end of each study day a hyperinsulinaemic-euglycaemic clamp was performed. Results: Four distinct levels of FFAs were obtained at the end of the lipid infusion period (FFALIPID: 0.03^0.00 vs: 0.49^0.04, 0.92^0.08 and 2.09^0.38 mmol/l; ANOVA P, 0.0001) and during hyperinsulinaemia (FFALIPIDþINSULIN: 0.02^0.00 vs: 0.34^0.03, 0.68^0.09 and 1.78^0.32 mmol/l; ANOVA P, 0.0001). Whereas, somatostatin infusion alone reduced ghrelin concentration by,67%, concomitant administration of increasing amounts of intralipid reduced cir-culating ghrelin by a further 14, 19 and 19 % respectively (change in ghrelin: 0.52^0.05 vs: 0.62^0.06, 0.72^0.09 and 0.71^0.05mg/l; ANOVA P 0.04). No further reduction in ghrelin concentration was observed during hyperinsulinaemia. Conclusion: FFA exposure between 0 and 1 mmol/l significantly suppresses ghrelin levels independent of ambient GH and insulin levels. European Journal of Endocrinology 154 667–67