Logo image
Back
Obesity-induced alterations to the immunoproteasome: a potential link to intramuscular lipotoxicity
Journal article   Peer reviewed

Obesity-induced alterations to the immunoproteasome: a potential link to intramuscular lipotoxicity

Emma Fletcher and Paul M Gordon
Applied physiology, nutrition, and metabolism, Vol.46(5), pp.485-493
05/2021
DOI: https://doi.org/10.1139/apnm-2020-0655
PMID: 33186056
Web of Science ID: WOS:000651030100009

Metrics

13 Record Views
5 Times Cited - Web of Science

Abstract

Although the mechanisms are unclear, inflammation and/or lipotoxicity likely contribute to obese muscle pathology. The immunoproteasome is known to respond to inflammation and oxidative damage and may aid muscle regeneration. We sought to determine whether diet-induced obesity (DIO) influences the immunoproteasome subunits LMP7 and MECL-1 in mouse muscle with and without exercise-induced muscle damage (EIMD). Muscle mass, regeneration, macrophage content and lipid peroxidation (8-isoprostane) were also assessed. Sixty male, 4-week-old C57BL/6J mice were fed a high-fat (HFD) or low-fat diet for 12 weeks. Mice were then subdivided into EIMD or no muscle damage (NMD) groups. The gastrocnemius muscle was excised 1 or 5 days after EIMD, producing 6 groups (n = 10/group). Body mass was greater; however, relative gastrocnemius mass was lower in HFD-fed mice. Despite no macrophage or MECL-1 alterations, LMP7 and 8-isoprostane were increased in obese mice in the NMD and 1 day post-EIMD groups. However, 8-isoprostane was reduced in obese mice 5 days post-EIMD, and accompanied by increased muscle LMP7, MECL-1 and macrophage content. Consequently, DIO may impair the immunoproteasome’s ability to control muscle lipid peroxidation but is reversed with eccentric exercise. Although muscle regeneration was unchanged, immunoproteasome dysregulation occurs in obese muscle and may contribute to muscle pathology. Novelty: DIO may impair the intramuscular immunoproteasome response to lipid peroxidation. Acute eccentric exercise may protect obese individuals from muscle lipotoxicity via immunoproteasome upregulation.

Details

Logo image