Long Term Metabolic Consequences of Exposures to Multipollutant Atmospheres in the Great Lakes Region

EPA Grant Number: R834797C003
Subproject: 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 - Main Campus
EPA Project Officer: Ilacqua, Vito
Project Period: December 1, 2010 through November 30, 2015 (Extended to December 31, 2016)
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

We have recently demonstrated that short-term exposure to concentrated ambient particulate matter (CAP) elicits the development of hypertension and insulin resistance (IR) that are facets of the cardiometabolic syndrome (CMS) often associated with obesity and diabetes. We hypothesize that long-term exposure to CAP, along with expose to the common gaseous air pollutant, ozone (O3), interacts with host factors such as diet and genetic susceptibility, resulting in the development of CMS. Project 3 is an integral component of our Center’s overarching theme that the major air pollutants, fine particulate matter (PM2.5) and O3), are 1) capable of eliciting multiple important adverse cardiometabolic health effects that are dependent on 2) the local multipollutant milieu, 3) an individual’s pre-existing cardiovascular (CV) and metabolic condition, and 4) the interactive toxicity of PM2.5 and O3 coexposure.

Approach:

Our proposed experiments are natural extensions of the human controlled exposure research outlined in Project 1 and the acute animal inhalation toxicology studies in Project 2. We will conduct long-term inhalation toxicology studies of obese and/or diabetic mice exposed to CAPs with or without O3. In Aim 1, simultaneous chronic exposure of mice to CAP from two locations in Columbus OH, representing nearroadway/residential or transported/regional multipollutant atmospheres, will be examined alone and in combination with a high fat chow diet (HFC). The impact of CAP on various biological measures of CMS (e.g., glucose/insulin homeostasis, adipokines, insulin signaling, inflammation in adipose tissue) along with an analysis of CAP concentrations and components associated with these induced health effects will be evaluated in HFC-fed mice and in mice with a genetic propensity for developing Type II diabetes (KKA/y). In Aim 2, we will investigate the effect of CAP and O3 coexposures on the temporal development of IR and inflammation in fat (adipose) and lung tissues of KKA/y mice. We will also assess dose-response relationships of CAP and O3 mixtures on IR and innate immune responses that are pivotal to the development of metabolic derangement characteristic of CMS. Based on data from Aims 1 and 2, we will design further experiments in Aim 3, which will help us to assess if and how CAP from multipollutant atmospheres may potentiate inflammatory cell (i.e., monocyte) activation and infiltration into various organs and tissues that may play important roles in mediating adverse systemic metabolic effects. We will contrast the results of health effect studies conducted at specified sites in Columbus, OH with those conducted in Dexter and Detroit, MI, to try to elucidate the components of these disparate multipollutant atmospheres that are most responsible for the enhancement of the CMS.

Expected Results:

Using state- of-the-art mobile inhalation exposure systems available at our laboratory (OASIS 1 and 2) and at Michigan State University (AirCARE 1 and 2), along with novel and high-resolution exposure characterization methods of our collaborators at The University of Michigan (Project 3) offers an unprecedented opportunity to elucidate relevant biological mechanisms responsible for the effects of ambient PM2.5 and O3 exposures on the pathogenesis of IR and other facets of the CMS. Insights from our studies will provide important guidance on how to better protect public health and susceptible populations, like those suffering from obesity and diabetes, from the harmful effects of environmental exposure to air pollutants in the Great Lakes Region and elsewhere.

Publications and Presentations:

Publications have been submitted on this subproject: View all 46 publications for this subprojectView all 144 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 35 journal articles for this subprojectView all 67 journal articles for this center

Supplemental Keywords:

obesity, insulin resistance, chronic exposure, inflammation, mice,, 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, cardiotoxicity

Progress and Final Reports:

2011 Progress Report
2012 Progress Report
2013 Progress Report
2014 Progress Report
2015 Progress Report
2016 Progress Report
Final Report


Main 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