Gormsen Lars C, Gjedsted Jakob, Gjedde Signe, Vestergaard Esben Thyssen, Christiansen Jens S, Jørgensen Jens Otto, Nielsen Søren, Møller Niels
Department M (endocrinology and diabetes), Aarhus University Hospital, DK-8000 Aarhus C, Denmark.
Eur J Endocrinol. 2006 May;154(5):667-73. doi: 10.1530/eje.1.02146.
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.
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.
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.
FFA exposure between 0 and 1 mmol/l significantly suppresses ghrelin levels independent of ambient GH and insulin levels.
食欲肽胃饥饿素的浓度受多种激素影响，这些激素也会影响游离脂肪酸（FFA）的循环水平。因此，本研究旨在确定FFA对循环中胃饥饿素的直接作用。
对8名体型偏瘦的健康男性进行4次检查，每次检查持续8小时，通过不同的输注速率（0、3、6和12微升/千克每分钟）静脉输注脂肪乳剂，以创造不同的血浆FFA浓度。通过给予阿昔莫司（250毫克）和生长抑素（300微克/小时）使胰岛素和生长激素水平保持恒定。在每个研究日结束时进行高胰岛素-正常血糖钳夹试验。
在脂肪乳剂输注期结束时获得了四个不同水平的FFA（FFA（脂质）：0.03±0.00对比：0.49±0.04、0.92±0.08和2.09±0.38毫摩尔/升；方差分析P<0.0001）以及在高胰岛素血症期间（FFA（脂质+胰岛素）：0.02±0.00对比：0.34±0.03、0.68±0.09和1.78±0.32毫摩尔/升；方差分析P<0.0001）。单独输注生长抑素可使胃饥饿素浓度降低约67%，同时给予递增剂量的脂肪乳剂分别使循环中的胃饥饿素进一步降低14%、19%和19%（胃饥饿素变化：0.52±0.05对比：0.62±0.06、0.72±0.09和0.71±0.05微克/升；方差分析P=0.04）。在高胰岛素血症期间未观察到胃饥饿素浓度进一步降低。
0至1毫摩尔/升的FFA暴露可显著抑制胃饥饿素水平，且与环境生长激素和胰岛素水平无关。
