title: Caspase-1 deficiency promotes high-fat diet-induced adipose tissue inflammation and the development of obesity.
abstract: Caspase-1 is a cysteine protease responsible for the processing of the proinflammatory cytokine interleukin-1β and activated by the formation of inflammasome complexes. Although several investigations have found a link between diet-induced obesity and caspase-1, the relationship remains controversial. Here, we found that mice deficient in caspase-1 were susceptible to high-fat diet-induced obesity with increased adiposity as well as normal lipid and glucose metabolism. Caspase-1 deficiency clearly promoted the infiltration of inflammatory macrophages and increased the production of C-C motif chemokine ligand 2 (CCL2) in the adipose tissue. The dominant cellular source of CCL2 was stromal vascular fraction rather than adipocytes in the adipose tissue. These findings demonstrate a critical role of caspase-1 in macrophage-driven inflammation in the adipose tissue and the development of obesity. These data provide novel insights into the mechanisms underlying inflammation in the pathophysiology of obesity.
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan; balhiro33@jichi.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Karasawa
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Fumitake
authors.initials: F
authors.lastname: Usui
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Endo
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Motoi
authors.initials: M
authors.lastname: Kobayashi
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Sadatomo
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nakamura
authors.affiliation: Division of Integrative Physiology, Jichi Medical University, Tochigi, Japan; and.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Division of Integrative Physiology, Jichi Medical University, Tochigi, Japan; and.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
authors.affiliation: Department of Microbiology, Hyogo College of Medicine, Nishinomiya, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Kasahara
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000473:pathology; D052242:Adiponectin / Q000276:immunology; D000273:Adipose Tissue / Q000276:immunology* / Q000473:pathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition; D020170:Caspase 1 / Q000235:genetics* / Q000276:immunology; D018932:Chemokine CCL2 / Q000276:immunology*; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005951:Glucose Tolerance Test; D007328:Insulin / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D020382:Interleukin-18 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D020738:Leptin / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055114:X-Ray Microtomography
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C587672:IL1B protein, mouse; D007328:Insulin; D020382:Interleukin-18; D053583:Interleukin-1beta; D015850:Interleukin-6; D020738:Leptin; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D018664:Interleukin-12; D007371:Interferon-gamma; D002784:Cholesterol; D020170:Caspase 1
keywords: adipocytes; cytokines: inflammasome; macrophages; stromal vascular fraction