title: Exposure to fine airborne particulate matter induces macrophage infiltration, unfolded protein response, and lipid deposition in white adipose tissue.
abstract: Recent epidemiological studies have suggested a link between exposure to ambient air-pollution and susceptibility to metabolic disorders such as Type II diabetes mellitus. Previously, we provided evidence that both short- and long-term exposure to concentrated ambient particulate matter with aerodynamic diameter <2.5 μm (PM2.5) induces multiple abnormalities associated with the pathogenesis of Type II diabetes mellitus, including insulin resistance, visceral adipose inflammation, brown adipose mitochondrial adipose changes, and hepatic endoplasmic reticulum (ER) stress. In this report, we show that chronic inhalation exposure to PM2.5 (10 months exposure) induces macrophage infiltration and Unfolded Protein Response (UPR), an intracellular stress signaling that regulates cell metabolism and survival, in mouse white adipose tissue in vivo. Gene expression studies suggested that PM2.5 exposure induces two distinct UPR signaling pathways mediated through the UPR transducer inositol-requiring 1α (IRE1α): 1) ER-associated Degradation (ERAD) of unfolded or misfolded proteins, and 2) Regulated IRE1-dependent Decay (RIDD) of mRNAs. Along with the induction of the UPR pathways and macrophage infiltration, expression of genes involved in lipogenesis, adipocyte differentiation, and lipid droplet formation was increased in the adipose tissue of the mice exposed to PM2.5. In vitro study confirmed that PM2.5 can trigger phosphorylation of the UPR transducer IRE1α and activation of macrophages. These results provide novel insights into PM2.5-triggered cell stress response in adipose tissue and increase our understanding of pathophysiological effects of particulate air pollution on the development of metabolic disorders.
authors.affiliation: Center for Molecular Medicine and Genetics, Wayne State University School of Medicine Detroit, MI 48201, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Mendez
authors.forename: Ze
authors.initials: Z
authors.lastname: Zheng
authors.forename: Zhongjie
authors.initials: Z
authors.lastname: Fan
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Sun
authors.forename: Kezhong
authors.initials: K
authors.lastname: Zhang
keywords: Ambient particulate matter; PM2.5; lipid metabolism; unfolded protein response; white adipose tissue