Clemente-Postigo, MercedesOliva-Olivera, WilfredoCoin-Aragüez, LeticiaRamos-Molina, BrunoGiraldez-Perez, Rosa MaríaLhamyani, SaidAlcaide-Torres, JuanPerez-Martinez, PabloEl Bekay, RajaaCardona, FernandoTinahones, Francisco J2023-01-252023-01-252018-11-13http://hdl.handle.net/10668/13178Impaired 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.enfatty acid binding proteinhuman adipose tissuehuman obesityleptinlipopolysaccharidesAdipocytesAdipose TissueAdultEndotoxemiaFatty Acid Synthase, Type IFatty Acid-Binding ProteinsFemaleGastrointestinal MicrobiomeGene ExpressionHumansInflammationIntra-Abdominal FatLeptinLipogenesisLipopolysaccharidesMaleMiddle AgedObesityPPAR gammaStearoyl-CoA DesaturaseSterol Regulatory Element Binding Protein 1Subcutaneous Fatresearch article30422702open access10.1152/ajpendo.00277.20181522-1555https://journals.physiology.org/doi/pdf/10.1152/ajpendo.00277.2018