Department of Clinical and Biological Sciences, Internal Medicine Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
Obesity (Silver Spring). 2010 Apr;18(4):788-97. doi: 10.1038/oby.2009.302. Epub 2009 Oct 15.
Central obesity shows impaired platelet responses to the antiaggregating effects of nitric oxide (NO), prostacyclin, and their effectors--guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP). The influence of weight loss on these alterations is not known. To evaluate whether a diet-induced body-weight reduction restores platelet sensitivity to the physiological antiaggregating agents and reduces platelet activation in subjects affected by central obesity, we studied 20 centrally obese subjects before and after a 6-month diet intervention aiming at reducing body weight by 10%, by measuring (i) insulin sensitivity (homeostasis model assessment of insulin resistance (HOMA(IR))); (ii) plasma lipids; (iii) circulating markers of inflammation of adipose tissue and endothelial dysfunction, and of platelet activation (i.e., soluble CD-40 ligand (sCD-40L) and soluble P-selectin (sP-selectin)); (iv) ability of the NO donor sodium nitroprusside (SNP), the prostacyclin analog Iloprost and the cyclic nucleotide analogs 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) to reduce platelet aggregation in response to adenosine-5-diphosphate (ADP); and (v) ability of SNP and Iloprost to increase cGMP and cAMP. The 10 subjects who reached the body-weight target showed significant reductions of insulin resistance, adipose tissue, endothelial dysfunction, and platelet activation, and a significant increase of the ability of SNP, Iloprost, 8-Br-cGMP, and 8-Br-cAMP to reduce ADP-induced platelet aggregation and of the ability of SNP and Iloprost to increase cyclic nucleotide concentrations. No change was observed in the 10 subjects who did not reach the body-weight target. Changes of platelet function correlated with changes of HOMA(IR). Thus, in central obesity, diet-induced weight loss reduces platelet activation and restores the sensitivity to the physiological antiaggregating agents, with a correlation with improvements in insulin sensitivity.
中心性肥胖会导致血小板对一氧化氮（NO）、前列环素及其效应物——环磷酸鸟苷（cGMP）和环磷酸腺苷（cAMP）的抗聚集作用的反应受损。目前尚不清楚体重减轻对这些变化的影响。为了评估饮食引起的体重减轻是否能恢复血小板对生理抗聚集剂的敏感性并减少中心性肥胖患者的血小板活化，我们在 20 名中心性肥胖患者进行了为期 6 个月的饮食干预，目标是减轻体重 10%，在此期间，我们测量了：（i）胰岛素敏感性（稳态模型评估的胰岛素抵抗（HOMA(IR)））；（ii）血浆脂质；（iii）脂肪组织和内皮功能障碍以及血小板活化的循环炎症标志物，即可溶性 CD40 配体（sCD-40L）和可溶性 P 选择素（sP-selectin）；（iv）NO 供体硝普钠（SNP）、前列环素类似物伊洛前列素和环核苷酸类似物 8-溴鸟苷 3'，5'-环磷酸（8-Br-cGMP）和 8-溴腺苷 3'，5'-环磷酸（8-Br-cAMP）降低血小板对二磷酸腺苷（ADP）的聚集作用的能力；以及（v）SNP 和伊洛前列素增加环鸟苷酸（cGMP）和环腺苷酸（cAMP）的能力。达到体重目标的 10 名患者表现出胰岛素抵抗、脂肪组织、内皮功能障碍和血小板活化显著降低，SNP、伊洛前列素、8-Br-cGMP 和 8-Br-cAMP 降低 ADP 诱导的血小板聚集的能力以及 SNP 和伊洛前列素增加环核苷酸浓度的能力显著增加。未达到体重目标的 10 名患者没有观察到变化。血小板功能的变化与 HOMA(IR)的变化相关。因此，在中心性肥胖中，饮食引起的体重减轻可降低血小板活化并恢复对生理抗聚集剂的敏感性，与胰岛素敏感性的改善相关。
