Exposure to fine airborne particulate matter induces macrophage infiltration, unfolded protein response, and lipid deposition in white adipose tissue.

摘要: Recent epidemiological studies have suggested a link between exposure to ambient air-pollution and susceptibility metabolic disorders such as Type II diabetes mellitus. Previously, we provided evidence that both short- long-term concentrated particulate matter with aerodynamic diameter <2.5 μm (PM2.5) induces multiple abnormalities associated the pathogenesis of mellitus, including insulin resistance, visceral adipose inflammation, brown mitochondrial changes, hepatic endoplasmic reticulum (ER) stress. In this report, show chronic inhalation PM2.5 (10 months exposure) macrophage infiltration Unfolded Protein Response (UPR), an intracellular stress signaling regulates cell metabolism survival, in mouse white tissue vivo. Gene expression two distinct UPR pathways mediated through transducer inositol-requiring 1α (IRE1α): 1) ER-associated Degradation (ERAD) unfolded or misfolded proteins, 2) Regulated IRE1-dependent Decay (RIDD) mRNAs. Along induction infiltration, genes involved lipogenesis, adipocyte differentiation, lipid droplet formation was increased mice exposed PM2.5. vitro study confirmed can trigger phosphorylation IRE1α activation macrophages. These results provide novel insights into PM2.5-triggered response increase our understanding pathophysiological effects air pollution on development disorders.