Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Department of Medical-Surgical Sciences and Bio-Technologies, Sapienza University of Rome, 00161 Rome, Italy.
Nutrients. 2018 Apr 23;10(4):526. doi: 10.3390/nu10040526.
Neurotensin (NT) is a 13-amino acid peptide localized in the neuroendocrine cells of the small intestine, which promotes fat absorption and fatty acids translocation in response to lipid ingestion. NT-knock-out mice fed with a high-fat diet are protected from obesity, fatty liver, and the development of insulin-resistance. In humans, higher plasma levels of pro-NT, which is the stable circulating precursor of NT, predict obesity, type 2 diabetes (T2D), and cardiovascular disease. In obesity, the presence of visceral adipose tissue (VAT) inflammation leads to unfavorable metabolic outcomes and is associated with the development of T2D and non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the relationship between plasma pro-NT levels and the presence of VAT inflammation in biopsies from 40 morbidly obese subjects undergoing bariatric surgery. We demonstrated that higher proNT levels are significantly associated with greater macrophages infiltration, HIF-1α, WISP-1, and UNC5B expression in VAT (all < 0.01) due to the diagnosis of T2D and NAFLD. The overall results show that, in obesity, pro-NT is a biomarker of VAT inflammation and insulin-resistance. Additionally, NT may be involved in the development of dysmetabolic conditions likely mediated by increased gut fat absorption and the presence of a proinflammatory milieu in the adipose tissue.
神经降压素（NT）是一种 13 个氨基酸的肽，定位于小肠的神经内分泌细胞中，可促进脂肪吸收和脂肪酸易位，以响应脂质摄入。用高脂肪饮食喂养的神经降压素敲除小鼠可预防肥胖、脂肪肝和胰岛素抵抗的发生。在人类中，前神经降压素（pro-NT），即 NT 的稳定循环前体，其血浆水平升高可预测肥胖、2 型糖尿病（T2D）和心血管疾病。在肥胖症中，内脏脂肪组织（VAT）炎症的存在会导致不良的代谢后果，并与 T2D 和非酒精性脂肪肝（NAFLD）的发生有关。在这项研究中，我们调查了 40 名接受减肥手术的病态肥胖患者活检中血浆 pro-NT 水平与 VAT 炎症之间的关系。我们证明，由于 T2D 和 NAFLD 的诊断，更高的 proNT 水平与 VAT 中巨噬细胞浸润、HIF-1α、WISP-1 和 UNC5B 表达的增加显著相关（均 < 0.01）。总体结果表明，在肥胖症中，pro-NT 是 VAT 炎症和胰岛素抵抗的生物标志物。此外，NT 可能参与了代谢紊乱的发展，可能是通过增加肠道脂肪吸收和脂肪组织中存在促炎环境介导的。
