title: Immunoproteasome subunit LMP7 Deficiency Improves Obesity and Metabolic Disorders.
abstract: Inflammation plays an important role in the development of obesity and metabolic disorders; however, it has not been fully understood how inflammation occurs and is regulated in their pathogenesis. Low-molecular mass protein-7 (LMP7) is a proteolytic subunit of the immunoproteasome that shapes the repertoire of antigenic peptides on major histocompatibility complex class I molecule. In this study, we investigated the role of LMP7 in the development of obesity and metabolic disorders using LMP7-deficient mice. LMP7 deficiency conveyed resistant to obesity, and improved glucose intolerance and insulin sensitivity in mice fed with high-fat diet (HFD). LMP7 deficiency decreased pancreatic lipase expression, increased fecal lipid contents, and inhibited the increase of plasma triglyceride levels upon oral oil administration or HFD feeding. Using bone marrow-transferred chimeric mice, we found that LMP7 in both bone marrow- and non-bone marrow-derived cells contributes to the development of HFD-induced obesity. LMP7 deficiency decreased inflammatory responses such as macrophage infiltration and chemokine expression while it increased serum adiponection levels. These findings demonstrate a novel role for LMP7 and provide new insights into the mechanisms underlying inflammation in the pathophysiology of obesity and metabolic disorders.
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
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: Fumitake
authors.initials: F
authors.lastname: Usui
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: Akira
authors.initials: A
authors.lastname: Kawashima
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Koumei
authors.initials: K
authors.lastname: Shirasuna
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Division of Inflammation Research, Center for Molecular Medicine, Jichi Medical University, Tochigi, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Komada
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: Yoshiko
authors.initials: Y
authors.lastname: Mizushina
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: Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University, Tochigi, Japan.
authors.forename: Yusaku
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Division of Integrative Physiology, Department of Physiology, Jichi Medical University, Tochigi, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yada
authors.affiliation: Department of Pathology, The Johns Hopkins School of Medicine, USA.
authors.forename: Patrizio
authors.initials: P
authors.lastname: Caturegli
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: D052242:Adiponectin / Q000097:blood; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D016026:Bone Marrow Transplantation; D018925:Chemokines / Q000378:metabolism; D059305:Diet, High-Fat; D004734:Energy Metabolism; D007333:Insulin Resistance; D008049:Lipase / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D008659:Metabolic Diseases / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D010179:Pancreas / Q000201:enzymology; D046988:Proteasome Endopeptidase Complex / Q000172:deficiency / Q000235:genetics*; D050507:Subcutaneous Fat, Abdominal / Q000000981:diagnostic imaging; D014280:Triglycerides / Q000097:blood; D055114:X-Ray Microtomography
chemical_list: D052242:Adiponectin; D015703:Antigens, CD; D018925:Chemokines; D014280:Triglycerides; D008049:Lipase; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex