title: Obesity-induced endoplasmic reticulum stress causes chronic inflammation in adipose tissue.
abstract: Adipose tissue plays a central role in maintaining metabolic homeostasis under normal conditions. Metabolic diseases such as obesity and type 2 diabetes are often accompanied by chronic inflammation and adipose tissue dysfunction. In this study, we observed that endoplasmic reticulum (ER) stress and the inflammatory response occurred in adipose tissue of mice fed a high-fat diet for a period of 16 weeks. After 16 weeks of feeding, ER stress markers increased and chronic inflammation occurred in adipose tissue. We found that ER stress is induced by free fatty acid (FFA)-mediated reactive oxygen species (ROS) generation and up-regulated gene expression of inflammatory cytokines in 3T3-L1 adipocytes. Oral administration to obese mice of chemical chaperons, which alleviate ER stress, improved chronic inflammation in adipose tissue, followed by the suppression of increased body weight and improved insulin signaling. These results indicate that ER stress plays important pathophysiological roles in obesity-induced adipose tissue dysfunction.
authors.affiliation: Department of Biochemistry, Institute of Biomedical & Health Science, University of Hiroshima, Minami-ku, Hiroshima, Japan.
authors.forename: Noritaka
authors.initials: N
authors.lastname: Kawasaki
authors.forename: Rie
authors.initials: R
authors.lastname: Asada
authors.forename: Atsushi
authors.initials: A
authors.lastname: Saito
authors.forename: Soshi
authors.initials: S
authors.lastname: Kanemoto
authors.forename: Kazunori
authors.initials: K
authors.lastname: Imaizumi
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000378:metabolism*; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002082:Butylamines / Q000494:pharmacology; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D059305:Diet, High-Fat; D059865:Endoplasmic Reticulum Stress; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D007328:Insulin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: C121358:4-phenylbutylamine; D002082:Butylamines; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D017382:Reactive Oxygen Species; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine