title: Adipocyte inflammation is essential for healthy adipose tissue expansion and remodeling.
abstract: Chronic inflammation constitutes an important link between obesity and its pathophysiological sequelae. In contrast to the belief that inflammatory signals exert a fundamentally negative impact on metabolism, we show that proinflammatory signaling in the adipocyte is in fact required for proper adipose tissue remodeling and expansion. Three mouse models with an adipose tissue-specific reduction in proinflammatory potential were generated that display a reduced capacity for adipogenesis in vivo, while the differentiation potential is unaltered in vitro. Upon high-fat-diet exposure, the expansion of visceral adipose tissue is prominently affected. This is associated with decreased intestinal barrier function, increased hepatic steatosis, and metabolic dysfunction. An impaired local proinflammatory response in the adipocyte leads to increased ectopic lipid accumulation, glucose intolerance, and systemic inflammation. Adipose tissue inflammation is therefore an adaptive response that enables safe storage of excess nutrients and contributes to a visceral depot barrier that effectively filters gut-derived endotoxin.
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wernstedt Asterholm
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Tao
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA.
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Morley
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA.
authors.forename: Qiong A
authors.initials: QA
authors.lastname: Wang
authors.affiliation: Facultad de Medicina, Universidad Catolica del Maule, Avenida San Miguel 3605, Talca, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Delgado-Lopez
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA.
authors.forename: Zhao V
authors.initials: ZV
authors.lastname: Wang
authors.affiliation: Department of Internal Medicine, Touchstone Diabetes Center, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA; Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA. Electronic address: philipp.scherer@utsouthwestern.edu.
authors.forename: Philipp E
authors.initials: PE
authors.lastname: Scherer
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D052242:Adiponectin / Q000378:metabolism; D052436:Adipose Tissue, White / Q000187:drug effects / Q000378:metabolism*; D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D059305:Diet, High-Fat; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology
chemical_list: D052242:Adiponectin; D000322:Adrenergic Agonists; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D020738:Leptin; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D000685:Serum Amyloid A Protein; D014409:Tumor Necrosis Factor-alpha