New insight into the mechanisms of ectopic fat deposition improvement after bariatric surgery
New insight into the mechanisms of ectopic fat deposition improvement after bariatric surgery
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DOI：
10.1038/s41598-019-53702-4
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发表时间：
2019-11-21
影响因子：
4.6
通讯作者：
Casella, Giovanni
中科院分区：
文献类型：
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作者：
Angelini, Giulia;Gissey, Lidia Castagneto;Casella, Giovanni
非酒精性脂肪性肝病（NAFLD）在肥胖患者中很常见，是糖尿病及其并发症发生的主要危险因素。减肥手术逆转了NAFLD的肝脏特征。然而，其作用机制仍然难以捉摸。我们对袖状胃切除术（SG）后肥胖啮齿动物和人类NAFLD和胰岛素抵抗改善的机制进行了全面分析。SG改善胰岛素敏感性，减少肝脏和单核细胞脂肪堆积。重要的是，单核细胞中的脂肪积累与肝细胞中的脂肪积累相当，这表明单核细胞中的Plin2水平可能是诊断NAFLD的非侵入性标志物。体外和体内研究均证明了肝功能和胰岛素敏感性的有效代谢再生。具体而言，SG通过增强AMP活化蛋白激酶（AMPK）磷酸化和伴侣介导的自噬（CMA）（转化为Plin2包被脂滴的去除）显著改善NAFLD。这导致脂肪分解增加和肝脏胰岛素抵抗的特异性改善。阐明肥胖者肝脏代谢受损的机制将有助于设计预防和治疗NAFLD的新策略。
Non-alcoholic fatty-liver disease (NAFLD) is frequent in obese patients and represents a major risk factor for the development of diabetes and its complications. Bariatric surgery reverses the hepatic features of NAFLD. However, its mechanism of action remains elusive. We performed a comprehensive analysis of the mechanism leading to the improvement of NAFLD and insulin resistance in both obese rodents and humans following sleeve-gastrectomy (SG). SG improved insulin sensitivity and reduced hepatic and monocyte fat accumulation. Importantly, fat accumulation in monocytes was well comparable to that in hepatocytes, suggesting that Plin2 levels in monocytes might be a non-invasive marker for the diagnosis of NAFLD. Both in vitro and in vivo studies demonstrated an effective metabolic regeneration of liver function and insulin sensitivity. Specifically, SG improved NAFLD significantly by enhancing AMP-activated protein kinase (AMPK) phosphorylation and chaperone-mediated autophagy (CMA) that translate into the removal of Plin2 coating lipid droplets. This led to an increase in lipolysis and specific amelioration of hepatic insulin resistance. Elucidating the mechanism of impaired liver metabolism in obese subjects will help to design new strategies for the prevention and treatment of NAFLD.