Decreased proteasomal function exacerbates ER stress-induced chronic inflammation in obese adipose tissue

This study employed a mouse model with decreased proteasomal function that exhibits age-related phenotypes to investigate the impact of adipocyte senescence on WAT inflammation. Transgenic mice expressing proteasomal subunit β5t with weak chymotrypsin-like activity suffer from reduced lifespan and develop age-related phenotypes. Mice fed with a high-fat diet (HFD) and suffering proteasomal dysfunction exhibited increased WAT inflammation, increased infiltration of pro-inflammatory M1-like macrophages, and increased pro-inflammatory adipocytokines like monocyte chemoattractant protein-1, plasminogen activator inhibitor-1, and tumor necrosis factor αwhich are all associated with activation of endoplasmic reticulum (ER) stress-related pathways. Impaired proteasomal activity also activated ER stress-related molecules and induced expression of pro-inflammatory adipocytokines in adipocyte-like cells differentiated from 3T3-L1 cells. Collective evidence suggests that impaired proteasomal activity increases ER stress and that subsequent inflammatory pathways play pivotal roles in WAT inflammation. Since proteasomal function declines with age, age-related proteasome impairment may be involved in obesity-related inflammation among the elderly.PMID:38423355 | DOI:10.1016/j.ajpath.2024.02.007
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research