| First Author | Liu C | Year | 2014 |
| Journal | Part Fibre Toxicol | Volume | 11 |
| Pages | 53 | PubMed ID | 25358444 |
| Mgi Jnum | J:319109 | Mgi Id | MGI:6862743 |
| Doi | 10.1186/s12989-014-0053-5 | Citation | Liu C, et al. (2014) Central IKKbeta inhibition prevents air pollution mediated peripheral inflammation and exaggeration of type II diabetes. Part Fibre Toxicol 11:53 |
| abstractText | BACKGROUND: Prior experimental and epidemiologic data support a link between exposure to fine ambient particulate matter (<2.5 mum in aerodynamic diameter, PM2.5) and development of insulin resistance/Type II diabetes mellitus (Type II DM). We investigated the role of hypothalamic inflammation in PM2.5-mediated diabetes development. METHODS: KKay mice, a genetically susceptible model of Type II DM, were assigned to either concentrated PM2.5 or filtered air (FA) for 4-8 weeks via a versatile aerosol concentrator and exposure system, or administered intra-cerebroventricular with either IKKbeta inhibitor (IMD-0354) or TNFalpha antibody (infliximab) for 4-5 weeks simultaneously with PM2.5 exposure. Glucose tolerance, insulin sensitivity, oxygen consumption and heat production were evaluated. At euthanasia, blood, spleen, visceral adipose tissue and hypothalamus were collected to measure inflammatory cells using flow cytometry. Standard immunohistochemical methods and quantitative PCR were used to assess targets of interest. RESULTS: PM2.5 exposure led to hyperglycemia and insulin resistance, which was accompanied by increased hypothalamic IL-6, TNFalpha, and IKKbeta mRNA expression and microglial/astrocyte reactivity. Targeting the NFkappaB pathway with intra-cerebroventricular administration of an IKKbeta inhibitor [IMD-0354, n = 8 for each group)], but not TNFalpha blockade with infliximab [(n = 6 for each group], improved glucose tolerance, insulin sensitivity, rectified energy homeostasis (O2 consumption, CO2 production, respiratory exchange ratio and heat generation) and reduced peripheral inflammation in response to PM2.5. CONCLUSIONS: Central inhibition of IKKbeta prevents PM2.5 mediated peripheral inflammation and exaggeration of type II diabetes. These results provide novel insights into how air pollution may mediate susceptibility to insulin resistance and Type II DM. |
