St-Pierre David H, Bastard Jean-Philippe, Coderre Lise, Brochu Martin, Karelis Antony D, Lavoie Marie-Eve, Malita Florin, Fontaine Jonathan, Mignault Diane, Cianflone Katherine, Imbeault Pascal, Doucet Eric, Rabasa-Lhoret Rémi
Département de Nutrition, Université de Montréal, Montréal, Québec, Canada, H3T 1A8.
Eur J Endocrinol. 2007 Oct;157(4):419-26. doi: 10.1530/EJE-07-0038.
Recent reports have suggested that the existence of associations between hormonal dysregulation and chronic upregulation of inflammatory markers, which may cause obesity-related disturbances. Thus, we examined whether acylated ghrelin (AcylG) and total ghrelin (TotG) levels could be associated with the following inflammatory markers: C-reactive protein (CRP), tumor necrosis factor alpha (TNF-alpha), and soluble TNF receptor 1 (sTNF-R1).
Cross-sectional study consisting of 50 overweight and obese postmenopausal women.
AcylG and TotG levels were assessed at 0, 60, 160, 170, and 180 min of the euglycemic/hyperinsulinemic clamp (EHC). We evaluated insulin sensitivity, body composition, and blood lipid profiles as well as fasting concentrations of CRP, TNF-alpha, and sTNF-R1.
In fasting conditions, sTNF-R1 was negatively correlated with AcylG (r = -0.48, P < 0.001) levels. In addition, AcylG/TotG was associated negatively with sTNF-R1 (r = -0.44, P = 0.002) and positively with TNF-alpha (r = 0.38, P = 0.009) values. During the EHC, TotG (at all time points) and AcylG (at 60 and 160 min) values were significantly decreased from fasting concentrations. AcylG maximal reduction and area under the curve (AUC) values were correlated to sTNF-R1 (r = -0.35, P = 0.02 and r = -0.34, P = 0.02, respectively). Meanwhile, the AcylG/TotG AUC ratio was associated negatively with sTNF-R1 (r = -0.29, P < 0.05) and positively with TNF-alpha (r = 0.36, P = 0.02). Following adjustments for total adiposity, sTNF-R1 remained correlated with fasting and maximal reduction AcylG values. Similarly, AcylG/TotG ratios remained significantly correlated with sTNF-R1 and TNF-alpha. Importantly, 23% of the variation in sTNF-R1 was independently predicted by fasting AcylG.
These results are the first to suggest that both fasting and EHC-induced AcylG profiles are correlated with fasting values of sTNF-R1, a component of the TNF-alpha system. Thus, AcylG may act, at least in part, as one mediator of chronic inflammatory activity in human obesity.
最近的报告表明，激素失调与炎症标志物的慢性上调之间存在关联，这可能导致与肥胖相关的紊乱。因此，我们研究了酰化胃饥饿素（AcylG）和总胃饥饿素（TotG）水平是否与以下炎症标志物相关：C反应蛋白（CRP）、肿瘤坏死因子α（TNF-α）和可溶性TNF受体1（sTNF-R1）。
对50名超重和肥胖的绝经后女性进行横断面研究。
在正常血糖/高胰岛素钳夹试验（EHC）的0、60、160、170和180分钟时评估AcylG和TotG水平。我们评估了胰岛素敏感性、身体成分和血脂谱以及CRP、TNF-α和sTNF-R1的空腹浓度。
在空腹条件下，sTNF-R1与AcylG水平呈负相关（r = -0.48，P < 0.001）。此外，AcylG/TotG与sTNF-R1呈负相关（r = -0.44，P = 0.002），与TNF-α呈正相关（r = 0.38，P = 0.009）。在EHC期间，TotG（在所有时间点）和AcylG（在60和160分钟）的值与空腹浓度相比显著降低。AcylG的最大降幅和曲线下面积（AUC）值与sTNF-R1相关（分别为r = -0.35，P = 0.02和r = -0.34，P = 0.02）。同时，AcylG/TotG的AUC比值与sTNF-R1呈负相关（r = -0.29，P < 0.05），与TNF-α呈正相关（r = 0.36，P = 0.02）。在对总体肥胖进行调整后，sTNF-R1仍与空腹和最大降幅的AcylG值相关。同样，AcylG/TotG比值仍与sTNF-R1和TNF-α显著相关。重要的是，空腹AcylG独立预测了sTNF-R1中23%的变异。
这些结果首次表明，空腹和EHC诱导的AcylG谱均与TNF-α系统成分sTNF-R1的空腹值相关。因此，AcylG可能至少部分地作为人类肥胖中慢性炎症活动的一种介质。
