氧化型低密度脂蛋白增加缺氧诱导的人内脏脂肪细胞的促炎特征。

Oxidized LDL Increase the Proinflammatory Profile of Human Visceral Adipocytes Produced by Hypoxia.

作者信息

Santiago-Fernández Concepción, Martín-Reyes Flores, Tome Monica, Gutierrez-Repiso Carolina, Fernandez-Garcia Diego, Ocaña-Wilhelmi Luis, Rivas-Becerra Jose, Tatzber Franz, Pursch Edith, Tinahones Francisco J, García-Fuentes Eduardo, Garrido-Sánchez Lourdes

机构信息

Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga (IBIMA)/Universidad de Málaga, Hospital Universitario Virgen de la Victoria, 29010 Málaga, Spain.

Unidad de Gestión Clínica de Endocrinología y Nutrición, Hospital Regional Universitario, 29010 Málaga, Spain.

出版信息

Biomedicines. 2021 Nov 18;9(11):1715. doi: 10.3390/biomedicines9111715.

BACKGROUND

Little is known about the effects of hypoxia on scavenger receptors (SRs) levels in adipocytes. We analyzed the effect of morbid obesity and hypoxia on SRs and inflammation markers in human visceral adipocytes and whether ox-LDL modify the inflammatory profile produced by hypoxia.

METHODS

We studied in 17 non-obese and 20 subjects with morbid obesity (MO) the mRNA expression of HIF-1α, SRs (LOX-1, MSR1, CL-P1 and CXCL16), IL6 and TNFα in visceral adipocytes and the effect of hypoxia with or without ox-LDL on visceral in vitro-differentiated adipocytes (VDA).

RESULTS

HIF-1α, TNFα, IL6, LOX-1, MSR1 and CXCL16 expression in adipocytes was increased in MO when compared with those in non-obese subjects ( < 0.05). The expression of most of the inflammatory markers and SRs gene correlated with HIF-1α. In VDA, hypoxia increased TNFα, IL6, MSR1, CXCL16 and CL-P1 ( < 0.05) in non-obese subjects, and TNFα, IL6, MSR1 and CXCL16 ( < 0.05) in MO. Silencing HIF-1α prevented the increase of TNFα, IL6, LOX-1, MSR1, CL-P1 and CXCL16 expression ( < 0.05). The combination of hypoxia and ox-LDL produced higher TNFα expression ( = 0.041).

CONCLUSIONS

Morbid obesity and hypoxia increased SRs and inflammatory markers in visceral adipocytes. In a hypoxic state, ox-LDL increased the proinflammatory response of visceral adipocytes to hypoxia.

背景

关于缺氧对脂肪细胞中清道夫受体（SRs）水平的影响，目前所知甚少。我们分析了病态肥胖和缺氧对人内脏脂肪细胞中SRs和炎症标志物的影响，以及氧化型低密度脂蛋白（ox-LDL）是否会改变缺氧所产生的炎症特征。

方法

我们研究了17名非肥胖者和20名病态肥胖（MO）受试者内脏脂肪细胞中缺氧诱导因子-1α（HIF-1α）、SRs（凝集素样氧化型低密度脂蛋白受体-1（LOX-1）、巨噬细胞清道夫受体1（MSR1）、C型凝集素结构域家族1成员P1（CL-P1）和CXC趋化因子配体16（CXCL16））、白细胞介素6（IL6）和肿瘤坏死因子α（TNFα）的mRNA表达，以及缺氧联合或不联合ox-LDL对体外分化的内脏脂肪细胞（VDA）的影响。

结果

与非肥胖受试者相比，MO患者脂肪细胞中HIF-1α、TNFα、IL6、LOX-1、MSR1和CXCL16的表达增加（P<0.05）。大多数炎症标志物和SRs基因的表达与HIF-1α相关。在VDA中，缺氧使非肥胖受试者的TNFα、IL6、MSR1、CXCL16和CL-P1增加（P<0.05），使MO患者的TNFα、IL6、MSR1和CXCL16增加（P<0.05）。沉默HIF-1α可阻止TNFα、IL6、LOX-1、MSR1、CL-P1和CXCL16表达的增加（P<0.05）。缺氧与ox-LDL联合作用使TNFα表达更高（P=0.041）。