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Free fatty acids decrease circulating ghrelin concentrations in humans

Department M (endocrinology and diabetes), Aarhus University Hospital, DK-8000 Aarhus C, Denmark

(Correspondence should be addressed to L C Gormsen; Email: lars.christian.gormsen{at}ki.au.dk)

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 12 µl/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 (300 µg/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 (FFA_LIPID: 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 (FFA_{LIPID+INSULIN}: 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 circulating 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 ± 0.05 µg/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.

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