Contribution of the immunoproteasome to the inflammatory phenotype observed in obese mice

Abstract

Abstract The immunoproteasome, a proteolytic machinery derived from the constitutive proteasome expressed predominantly in immune cells, plays a critical role in the regulation of T cell polarization that occurs in autoimmune and inflammatory diseases. Recently, it has been shown that inflammation contributes to the development of obesity and metabolic disorders. We found that LMP7, one of subunits in the immunoproteasome, is expressed in epididymal adipose tissue of obese mice. In this study, we assessed the role of LMP7 in the pathogenesis of murine obesity induced by high-fat diet (HFD). LMP7 deficiency conveyed resistant to obesity, and improved glucose intolerance and insulin sensitivity. Using bone marrow-transferred chimera, we found that LMP7 contributed to the development of obesity through involvement of both bone marrow- and non-bone marrow-derived cells. LMP7 deficiency decreased inflammatory responses, such as macrophage infiltration and chemokine expression, as well as increased serum adiponectin levels and decreased serum leptin levels. Overall, LMP7 deficiency in both bone marrow- and non-bone marrow-derived cells contributed to the suppression of the inflammatory responses in the HFD-induced obesity. We propose the immunoproteasome as a therapeutic target in inflammatory disorders.