2011 Progress Report: Long Term Metabolic Consequences of Exposures to Multipollutant Atmospheres in the Great Lakes Region
EPA Grant Number: R834797C003Subproject: this is subproject number 003 , established and managed by the Center Director under grant R834797
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Great Lakes Air Center for Integrative Environmental Research
Center Director: Harkema, Jack
Title: Long Term Metabolic Consequences of Exposures to Multipollutant Atmospheres in the Great Lakes Region
Investigators: Rajagopalan, Sanjay , Sun, Qinghua
Institution: The Ohio State University
EPA Project Officer: Chung, Serena
Project Period: December 1, 2010 through November 30, 2015 (Extended to December 31, 2016)
Project Period Covered by this Report: January 1, 2011 through July 31,2011
RFA: Clean Air Research Centers (2009) RFA Text | Recipients Lists
Research Category: Human Health , Air
Objective:
We recently have demonstrated that short-term exposure to inhaled concentrated airborne particulate (CAP) matter <2.5 microns (PM2.5) results in components of cardiometabolic syndrome (CMS), including development of hypertension and insulin resistance. In this project, we hypothesize that chronic inhalation of CAP in conjunction with gaseous components such as ozone from distinct multipollutant atmospheres synergistically interacts with diet and genetic susceptibility to influence development of CMS. Project 3 is an integral component of the overarching theme of this Center that primary air pollutants, fine PM (PM2.5) and ozone (O3), cause cardiometabolic health effects that are dependent on the local atmospheric multipollutant milieu, predisposing factors, and the interactive toxicity of multipollutant coexposure. The experiments proposed are natural extensions of human research outlined in Project 1 and acute experiments in Project 2 and will focus on conducting chronic inhalation toxicology studies in diet fed and genetic models of obesity/diabetes. In Aim 1, simultaneous chronic exposure to multipollutant CAP from two locations in Columbus, OH, representing near-roadside/traffic or remotely transported/aged emissions will be examined in combination with high fat chow (HFC). The impact of CAP on glucose/insulin homeostasis, adipokines, insulin signaling, adipose and pulmonary inflammation and an analysis of dose dependence and CAP components most likely associated with these effects will be evaluated in diet sensitive (C57Bl/6) and genetic models of Type II diabetes susceptibility (KKA/y). In Aim 2, we will investigate the effect of co-exposure of multipollutant CAP with ozone on the temporal development of insulin resistance and adipose/lung inflammation using the KKA/y model. We will assess dose response relationship of multipollutant-O3 mixture on insulin resistance measures (HOMA-IR and IPGTT) and novel mediators of innate immune, pivotal in the development of metabolic derangement. Based on data from Aims 1 and 2, we will design experiments in Aim 3, which will help us assess chronic effects of multipollutant CAP in potentiating inflammatory monocyte activation and infiltration into tissue niches as a central mechanism for mediating adverse metabolic effects of CAP. Using state of the art multiple exposure systems available at OSU (OASIS-1 and OASIS-2) and MI in conjunction with the resources available at the ECC, including the use of several novel high-time resolution exposure characterization methods, GLACIER offers an unprecedented opportunity to elucidate relevant mechanisms responsible for the effects of multipollutant CAP on the pathogenesis of insulin resistance and inflammation. The insights gleaned from the acute studies planned in Projects 1 and 2 in conjunction with chronic studies in Project 3, have significant public health ramifications and may eventually lead to policy changes to avert environmental exposure to PM2.5.
Progress Summary:
There have been no changes in study design. Due to the arrival of funds in April 2011, our time line for redesign of the chambers to accommodate simultaneous ozone exposure has been delayed. During the 7 months of activity of Year 1 for Project 3 (December 2010 - July 2011), we have successfully started the project. As planned, we have been working on the modification of our current exposure system in a new near-roadside facility in (OASIS-2) that will allow dual exposure of concentrated airborne particulate (CAP, PM2.5) and ozone (O3). This has been going well with successful completion of the project anticipated at the end of August. This will allow us to begin work on the combined exposure of CAP+ozone in susceptible models. On completion, we also will be able to examine exposure to CAP alone in two locations [OASIS-1 (mobile exposure lab) and 2] as we have planned. Simultaneously, there are several projects associated with the overall hypothesis in terms of air pollution on metabolic syndrome, including studying the impact of CAP on glucose/insulin homeostasis, adipokines, insulin signaling, adipose and pulmonary inflammation that we currently are working on to provide the best estimates of duration and dose of exposure planned in Aim 1. These experiments are crucial to our studies in diet sensitive (C57Bl/6) and genetic models of type II diabetes susceptibility (KKA/y) in Aim 1 and 2. We expect to have at least one manuscript published during Year 1.
Future Activities:
All aspects of the study protocol are approved by our IACUC. The mice are expected to be purchased and exposed as soon as the exposure system is in place at Polaris Exposure Facility (OASIS-2) in Columbus, OH, and we anticipate completing specific aim 1 (January 2012). Thereafter, we will begin work on specific aim 2.
Journal Articles:
No journal articles submitted with this report: View all 46 publications for this subprojectSupplemental Keywords:
Scientific Discipline, Air, ENVIRONMENTAL MANAGEMENT, air toxics, Health Risk Assessment, Biochemistry, Biology, Risk Assessment, ambient air quality, particulate matter, aerosol particles, susceptible populations, acute cardiovascualr effects, human exposure, physiology, cardiopulmonary, cardiotoxicityRelevant Websites:
http://greatlakesairresearchcenter.org/
Progress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R834797 Great Lakes Air Center for Integrative Environmental Research Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R834797C001 Cardiometabolic Effects of Exposure to Differing Mixtures and Concentrations of PM2.5 in Obese and Lean Adults
R834797C002 Cardiometabolic, Autonomic, and Airway Toxicity of Acute Exposures to PM2.5 from Multipollutant Atmospheres in the Great Lakes Region
R834797C003 Long Term Metabolic Consequences of Exposures to Multipollutant Atmospheres in the Great Lakes Region