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血管生成素样蛋白8(ANGPTL8)在人体脂肪组织中的表达及定位证据

Evidences for Expression and Location of ANGPTL8 in Human Adipose Tissue.

作者信息

Catalano-Iniesta Leonardo, Sánchez Robledo Virginia, Iglesias-Osma María Carmen, Galán Albiñana Amparo, Carrero Sixto, Blanco Enrique J, Carretero-Hernández Marta, Carretero José, García-Barrado María José

机构信息

Department of Physiology and Pharmacology, Faculty of Medicine, University of Salamanca, 38007 Salamanca, Spain.

Laboratory of Neuroendocrinology, Institute of Neurosciences of Castilla y León (INCyL), and Laboratory of Neuroendocrinology and Obesity, Institute of Biomedical Research of Salamanca (IBSAL), University of Salamanca, 38007 Salamanca, Spain.

出版信息

J Clin Med. 2020 Feb 13;9(2):512. doi: 10.3390/jcm9020512.

Abstract

The metabolism of triglycerides (TGs) is regulated, among others, by the lipoprotein lipase (LPL) that hydrolyses the TGs on endothelial cells. In turn, LPL is inhibited by the ANGPTLs family of proteins, such as ANGPTL3, 4, and, 8; the latter is the least known. In this work, we have tried to establish the expression and localisation of the Angiopoietin-like 8 (ANGPTL8) protein in the visceral adipose tissue (VAT) of morbid-obese and non-obese patients. 109 subjects (66 women and 43 men) undergoing laparoscopic surgery participated in this study. A blood sample and a portion of the VAT were obtained, and the patients were classified according to their Body Mass Index (BMI) as non-obese (19.5-30 kg/m) and morbid-obese (40-50 kg/m). No significant changes in ANGPTL8 plasma levels were determined by EIA in obese patients. The immunocytochemistry and Western blotting showed the presence of increased ANGPTL8 in morbid-obese patients ( < 0.05). In-situ hybridisation and a real time polymerase chain reaction (RT-PCR) confirmed that the mRNA that encodes ANGPTL8 was present in adipocytes, without differences in their nutritional state ( = 0.89), and even in the endothelial cells. Our data suggests that ANGPT8 plasmatic levels do not change significantly in patients with morbid obesity, although there is a modest difference related to gender. Besides, we demonstrate that in visceral adipose tissue, ANGPTL8 is well defined in the cytoplasm of adipocytes coexisting with perilipin-1 and its mRNA, also is present in endothelial cells. These findings suggest the possibility that among other functions, ANGPTL8 could perform either a paracrine and/or an endocrine role in the adipose tissue.

摘要

甘油三酯(TGs)的代谢受多种因素调节,其中脂蛋白脂肪酶(LPL)可在内皮细胞上水解TGs。反过来,LPL受到血管生成素样蛋白家族(ANGPTLs)的抑制,如ANGPTL3、4和8;其中ANGPTL8最不为人所知。在这项研究中,我们试图确定血管生成素样8(ANGPTL8)蛋白在病态肥胖和非肥胖患者内脏脂肪组织(VAT)中的表达和定位。109名接受腹腔镜手术的受试者(66名女性和43名男性)参与了本研究。采集了血样和一部分VAT,根据体重指数(BMI)将患者分为非肥胖(19.5 - 30 kg/m²)和病态肥胖(40 - 50 kg/m²)。通过酶免疫分析(EIA)测定,肥胖患者的ANGPTL8血浆水平无显著变化。免疫细胞化学和蛋白质印迹法显示,病态肥胖患者中ANGPTL8的含量增加(P < 0.05)。原位杂交和实时聚合酶链反应(RT-PCR)证实,编码ANGPTL8的mRNA存在于脂肪细胞中,无论其营养状态如何(P = 0.89),甚至在内皮细胞中也有。我们的数据表明,病态肥胖患者的ANGPT8血浆水平没有显著变化,尽管存在与性别相关的适度差异。此外,我们证明在内脏脂肪组织中,ANGPTL8在与脂肪周蛋白-1及其mRNA共存的脂肪细胞胞质中表达明确,也存在于内皮细胞中。这些发现表明,ANGPTL8除了其他功能外,还可能在脂肪组织中发挥旁分泌和/或内分泌作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/09bc/7074245/b567be27347c/jcm-09-00512-g001.jpg

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