title: Overexpression of TNF-α converting enzyme promotes adipose tissue inflammation and fibrosis induced by high fat diet.
abstract: Obesity is a state in which chronic low-grade inflammation persists in adipose tissues. Pro-inflammatory cytokines, including TNF-α, produced by adipose tissues have been implicated as active participants in the development of obesity-related diseases. Since TNF-α converting enzyme (TACE) is the major factor that induces soluble TNF-α, TACE has been noted as a pivotal regulator in this field. To reveal the role of TACE in adipose tissue inflammation, TACE-transgenic (TACE-Tg) and wild type (WT) mice were fed with high fat diet (HFD) or control diet for 16 weeks. At 13 weeks after the beginning of the diet, serum TNF-α and macrophage-related cytokine/chemokine levels were elevated in TACE-Tg mice fed with HFD (Tg-HFD mice), and the number of the so-called crown-like adipocyte was significantly increased in adipose tissues of Tg-HFD mice at the end of the experiment. Although macrophage infiltration was not detected in the adipose tissues at this time, fibrosis was observed around the crown-like adipocytes. These findings suggested that TACE overexpression induced macrophage infiltration and subsequent fibrosis in adipose tissues under HFD regimen. The collective evidence suggested that TACE could be a therapeutic target of HFD-induced obesity-related adipose tissue inflammation.
authors.affiliation: Graduate School of Health Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Utano
authors.initials: U
authors.lastname: Tomaru
authors.affiliation: Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Arina
authors.initials: A
authors.lastname: Miyoshi
authors.affiliation: Department of Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ito
authors.affiliation: Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Fukaya
authors.affiliation: Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Internal Medicine II, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.affiliation: Faculty of Health Sciences, Hokkaido University, Sapporo, Japan. Electronic address: aishizu@med.hokudai.ac.jp.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Ishizu
mesh_terms: D051722:ADAM Proteins / Q000096:biosynthesis*; D000072198:ADAM17 Protein; D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000378:metabolism; D015151:Immunoblotting; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606463:Adam17 protein, mouse
keywords: Adipose tissue inflammation; High fat diet; Obesity; TACE; TNF-α