Immunoproteasome subunit LMP7 Deficiency Improves Obesity and Metabolic Disorders

Hiroaki Kimura, Fumitake Usui, Tadayoshi Karasawa, Akira Kawashima, Koumei Shirasuna, Yoshiyuki Inoue, Takanori Komada, Motoi Kobayashi, Yoshiko Mizushina, Tadashi Kasahara, Koichi Suzuki, Yusaku Iwasaki, Toshihiko Yada, Patrizio Caturegli, Masafumi Takahashi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number15883
JournalScientific reports
Volume5
DOIs
StatePublished - Oct 30 2015

ASJC Scopus subject areas

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    Kimura, H., Usui, F., Karasawa, T., Kawashima, A., Shirasuna, K., Inoue, Y., Komada, T., Kobayashi, M., Mizushina, Y., Kasahara, T., Suzuki, K., Iwasaki, Y., Yada, T., Caturegli, P., & Takahashi, M. (2015). Immunoproteasome subunit LMP7 Deficiency Improves Obesity and Metabolic Disorders. Scientific reports, 5, [15883]. https://doi.org/10.1038/srep15883