title: Attenuation of obesity-induced adipose tissue inflammation in C3H/HeJ mice carrying a Toll-like receptor 4 mutation.
abstract: Obese adipose tissue is characterized by increased infiltration of macrophages, suggesting that they might represent an important source of inflammation. We have provided in vitro evidence that saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 (TLR4) to induce the inflammatory changes in macrophages. Here we show the attenuation of adipose tissue inflammation in C3H/HeJ mice carrying a functional mutation in the TLR4 gene relative to control C3H/HeN mice during a 16-week high-fat diet. We also find that adiponectin mRNA expression is significantly reduced by co-culture of hypertrophied 3T3-L1 adipocytes and C3H/HeN peritoneal macrophages, which is reversed, when co-cultured with C3H/HeJ peritoneal macrophages. This study provides in vivo evidence that TLR4 plays a role in obesity-related adipose tissue inflammation and thus helps to identify the therapeutic targets that may reduce obesity-induced inflammation and the metabolic syndrome.
authors.affiliation: Department of Molecular Medicine and Metabolism, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10 Kanda-surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.forename: Tae
authors.initials: T
authors.lastname: Mieda
authors.forename: Michiko
authors.initials: M
authors.lastname: Itoh
authors.forename: Yuri
authors.initials: Y
authors.lastname: Shimoda
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kamei
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D017667:Adipocytes / Q000276:immunology*; D000273:Adipose Tissue / Q000276:immunology*; D000818:Animals; D002478:Cells, Cultured; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009154:Mutation; D009765:Obesity / Q000150:complications* / Q000276:immunology*; D015434:Panniculitis / Q000209:etiology* / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology*
chemical_list: C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4