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.


METHODS
Eight lean, healthy men were examined for 8 h on four occasions using variable infusion rates (0, 3, 6 and 12 microl/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 microg/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 approximately 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 microg/l; ANOVA P = 0.04). No further reduction in ghrelin concentration was observed during hyperinsulinaemia.


CONCLUSIONS
FFA exposure between 0 and 1 mmol/l significantly suppresses ghrelin levels independent of ambient GH and insulin levels.
Gormsen
Lars C
LC
Department M (endocrinology and diabetes), Aarhus University Hospital, DK-8000 Aarhus C, Denmark. lars.christian.gormsen@ki.au.dk
Gjedsted
Jakob
J
Gjedde
Signe
S
Vestergaard
Esben Thyssen
ET
Christiansen
Jens S
JS
Jørgensen
Jens Otto
JO
Nielsen
Søren
S
Møller
Niels
N
D000328:Adult; D000925:Anticoagulants / Q000008:administration & dosage; D001786:Blood Glucose; D002096:C-Peptide / Q000097:blood; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000008:administration & dosage* / Q000097:blood*; D054439:Ghrelin; D015309:Glucose Clamp Technique; D006493:Heparin / Q000008:administration & dosage; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006946:Hyperinsulinism / Q000097:blood; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000097:blood; D008297:Male; D036361:Peptide Hormones / Q000097:blood*; D011719:Pyrazines / Q000008:administration & dosage; D013004:Somatostatin / Q000008:administration & dosage
D000925:Anticoagulants; D001786:Blood Glucose; D002096:C-Peptide; D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D054439:Ghrelin; D000960:Hypolipidemic Agents; D007328:Insulin; D036361:Peptide Hormones; D011719:Pyrazines; D019382:Human Growth Hormone; D013004:Somatostatin; D006493:Heparin; C027696:acipimox; D006854:Hydrocortisone