Pioglitazone in the treatment of NASH: the role of adiponectin
Pioglitazone in the treatment of NASH: the role of adiponectin
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DOI：
10.1111/j.1365-2036.2010.04405.x
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发表时间：
2010-09-15
影响因子：
7.6
通讯作者：
Cusi, K.
中科院分区：
文献类型：
--
作者：
Gastaldelli, A.;Harrison, S.;Cusi, K.
NASH患者血浆脂联素水平降低，噻唑烷二酮治疗期间组织学改善的机制仍知之甚少。目的评价吡格列酮治疗后血浆脂联素变化与代谢/组织学改善之间的关系。方法我们在47例NASH患者和20例对照组中测定：（i）空腹血糖、胰岛素、FFA和脂联素浓度;（ii）通过磁共振波谱分析的肝脂肪含量;和（iii）外周/肝胰岛素敏感性（通过双示踪口服葡萄糖耐量试验）。患者，然后用吡格列酮（45毫克/天）或安慰剂和所有的测量重复6 months.ResultsPatients与NASH的血浆脂联素水平下降独立的肥胖的存在。吡格列酮使血浆脂联素增加2.3倍，并改善胰岛素抵抗、葡萄糖耐量和葡萄糖清除率、脂肪变性和坏死性炎症（与安慰剂相比，所有P < 0.01-0.001）。在吡格列酮组，血浆脂联素与肝脏胰岛素敏感性和两个变量的变化显著相关（r = 0.52，P = 0.0001）（r = 0.44，P = 0.03）。脂联素浓度的增加也与组织学改善有关，特别是与肝脂肪变性有关（r =-0.46，P = 0.006）和坏死性炎症（r =-0.56，P < 0.0001），但重要的是，结论脂联素在肝脏水平具有重要的代谢作用，并且在吡格列酮治疗期间其增加对于逆转NASH患者的胰岛素抵抗和改善肝脏组织学至关重要。
P>BackgroundPlasma adiponectin is decreased in NASH patients and the mechanism(s) for histological improvement during thiazolidinedione treatment remain(s) poorly understood.AimTo evaluate the relationship between changes in plasma adiponectin following pioglitazone treatment and metabolic/histological improvement.MethodsWe measured in 47 NASH patients and 20 controls: (i) fasting glucose, insulin, FFA and adiponectin concentrations; (ii) hepatic fat content by magnetic resonance spectroscopy; and (iii) peripheral/hepatic insulin sensitivity (by double-tracer oral glucose tolerance test). Patients were then treated with pioglitazone (45 mg/day) or placebo and all measurements were repeated after 6 months.ResultsPatients with NASH had decreased plasma adiponectin levels independent of the presence of obesity. Pioglitazone increased 2.3-fold plasma adiponectin and improved insulin resistance, glucose tolerance and glucose clearance, steatosis and necroinflammation (all P < 0.01-0.001 vs. placebo). In the pioglitazone group, plasma adiponectin was significantly associated (r = 0.52, P = 0.0001) with hepatic insulin sensitivity and with the change in both variables (r = 0.44, P = 0.03). Increase in adiponectin concentration was related also to histological improvement, in particular, to hepatic steatosis (r = -0.46, P = 0006) and necroinflammation (r = -0.56, P < 0.0001) but importantly also to fibrosis (r = -0.29, P = 0.03).ConclusionsAdiponectin exerts an important metabolic role at the level of the liver, and its increase during pioglitazone treatment is critical to reverse insulin resistance and improve liver histology in NASH patients.