Unidad de Gestión Clínica Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga-IBIMA, Hospital Universitario Virgen de la Victoria/Universidad de Málaga. Málaga, Spain.
Centro de Investigación Biomédica En Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII) , Málaga , Spain.
Am J Physiol Endocrinol Metab. 2019 Feb 1;316(2):E319-E332. doi: 10.1152/ajpendo.00277.2018. Epub 2018 Nov 13.
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 ( SREBP1, 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.
脂肪组织（AT）的脂质处理和炎症功能受损与肥胖相关的代谢性疾病有关。肠道微生物群产生的循环脂多糖（LPSs）（代谢性内毒素血症），被认为是肥胖症低度炎症的触发因素，也可能导致 AT 功能障碍。然而，这一假说尚未在人类肥胖症中得到验证。为了分析代谢性内毒素血症与 AT 脂肪生成、脂质处理和炎症标志物之间的关系，我们招募了 33 名接受手术的肥胖症患者，并根据 LPS 水平进行分类。分析了内脏和皮下 AT 的基因和蛋白表达，并进行了脂肪细胞和 AT 的体外实验。与 LPS 水平较低的患者相比，具有高度代谢性内毒素血症的肥胖症患者的 AT 功能和脂肪生成的关键基因（SREBP1、FABP4、FASN 和 LEP）表达较低，但内脏和皮下 AT 的炎症基因表达较高。体外实验证实 LPS 可引起脂肪细胞和 AT 炎症，并下调 PPARG、SCD、FABP4、LEP 的表达和 LEP 分泌。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增加炎症来影响人类肥胖症中的 AT 生理学。
