1. Metabolic endotoxemia promotes adipose dysfunction and inflammation in human obesity
- Author
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Rosa M. Giráldez-Pérez, Fernando Cardona, Francisco J. Tinahones, Pablo Perez-Martinez, Mercedes Clemente-Postigo, Juan Alcaide-Torres, Wilfredo Oliva-Olivera, Leticia Coín-Aragüez, Rajaa El Bekay, Said Lhamyani, and Bruno Ramos-Molina
- Subjects
Leptin ,Lipopolysaccharides ,Male ,0301 basic medicine ,fatty acid binding protein ,Physiology ,Endocrinology, Diabetes and Metabolism ,Gene Expression ,Adipose tissue ,Gut flora ,Metabolic endotoxemia ,0302 clinical medicine ,Adipocytes ,Medicine ,biology ,Middle Aged ,Fatty Acid Synthase, Type I ,Adipose Tissue ,Female ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,Sterol Regulatory Element Binding Protein 1 ,Stearoyl-CoA Desaturase ,Adult ,medicine.medical_specialty ,Subcutaneous Fat ,030209 endocrinology & metabolism ,Inflammation ,Intra-Abdominal Fat ,Fatty Acid-Binding Proteins ,Fatty acid-binding protein ,human obesity ,03 medical and health sciences ,Physiology (medical) ,Internal medicine ,Humans ,Obesity ,human adipose tissue ,Human obesity ,business.industry ,Lipogenesis ,medicine.disease ,biology.organism_classification ,Endotoxemia ,Gastrointestinal Microbiome ,PPAR gamma ,030104 developmental biology ,Endocrinology ,business - Abstract
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.
- Published
- 2019