Metabolic endotoxemia promotes adipose dysfunction and inflammation in human obesity
Metabolic endotoxemia promotes adipose dysfunction and inflammation in human obesity
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DOI：
10.1152/ajpendo.00277.2018
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发表时间：
2019-02-01
影响因子：
5.1
通讯作者：
Tinahones, Francisco J.
中科院分区：
文献类型：
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作者：
Clemente-Postigo, Mercedes;Oliva-Olivera, Wilfredo;Tinahones, Francisco J.
脂肪组织（AT）脂质处理和炎症受损与肥胖相关的代谢疾病有关。来自肠道微生物群的循环脂多糖（LPS）（代谢性内毒素血症）被认为是肥胖症低度炎症的触发因素，也可能是AT功能障碍的原因。然而，这一假设尚未在人类肥胖中进行过探索。分析代谢性内毒素血症与脂肪生成、脂质处理和炎症的AT标志物之间的关系。招募了33名计划手术的肥胖患者，并根据其LPS水平进行分类。分析内脏和皮下AT基因和蛋白表达，并进行脂肪细胞和AT体外测定。患有高度代谢性内毒素血症的肥胖症受试者具有AT功能和脂肪生成的关键基因（SREBPI、FABP4、FABP5、FABP6）的较低表达。和LEP），但内脏和皮下AT中炎症基因的表达高于低LPS水平的受试者。体外实验证实，LPS负责脂肪细胞和AT炎症以及PPARG、SCD、FABP4和LEP表达和LEP分泌的下调。因此，代谢性内毒素血症通过降低参与AT脂质处理和功能的因子的表达以及通过增加炎症来影响人类肥胖中的AT生理学。
Impaired adipose tissue (AT) lipid handling and inflammation is associated with obesity-related metabolic diseases. Circulating lipopolysaccharides (LPSs) from gut microbiota (metabolic endotoxemia), proposed as a triggering factor for the low-grade inflammation in obesity, might also be responsible for AT dysfunction. Nevertheless, this hypothesis has not been explored in human obesity. To analyze the relationship between metabolic endotoxemia and AT markers for lipogenesis, lipid handling, and inflammation in human obesity. 33 patients with obesity scheduled for surgery were recruited and classified according to their LPS levels. Visceral and subcutaneous AT gene and protein expression were analyzed and adipocyte and AT in vitro assays performed. Subjects with obesity with a high degree of metabolic endotoxemia had lower expression of key genes for AT function and lipogenesis (SREBPI, FABP4, FASN. and LEP) but higher expression of inflammatory genes in visceral and subcutaneous AT than subjects with low LPS levels. In vitro experiments corroborated that LPS are responsible for adipocyte and AT inflammation and downregulation of PPARG, SCD, FABP4, and LEP expression and LEP secretion. Thus, metabolic endotoxemia influences AT physiology in human obesity by decreasing the expression of factors involved in AT lipid handling and function as well as by increasing inflammation.