School of Medicine

Wayne State University School of Medicine

WSU team identifies why air pollution raises metabolic disorder risk

Kezhong Zhang, Ph.D.

Kezhong Zhang, Ph.D.

A team led by the Wayne State University School of Medicine’s Kezhong Zhang, Ph.D., has discovered why people living in areas with higher than normal levels of air pollution are at increased risk of developing metabolic disorders such as type 2 diabetes, obesity and atherosclerosis, the thickening of artery walls.

The study pinpoints the stress mechanism that causes air pollution to impair both lipid and glucose metabolism and insulin action in the liver. The team expects the work to have a major impact on health policy decision-making, clinical disease diagnosis and treatment.

“Our study indicated that those who work under high levels of PM2.5 exposure, such as truck drivers and car industry employees, have much higher risk to developing metabolic disease, such as obesity and type 2 diabetes,” Dr. Zhang said. PM2.5 is airborne particulate matter with an aerodynamic diameter smaller than 2.5 micrometers. It’s a mix of particles and gases from gasoline and diesel engines, together with dust from roads, tires and brakes.

His team worked with other groups in the School of Medicine’s Center for Molecular Medicine and Genetics, as well as researchers at Ohio State University. Dr. Zhang, assistant professor of Molecular Medicine and Genetics and of Immunology and Microbiology, is the project’s principal investigator.

“PM2.5 particles are the major toxic components of air pollution. PM2.5 pollution has major impact on public health for the general population in urban areas, especially for those who live in areas of intensive traffic or industrial activity. Recent epidemiological studies and clinical observations suggested that populations under high levels of PM2.5 exposure have much higher risk to develop cardiovascular disease and metabolic disease,” he said.

The risk is through liver-associated inflammatory stress and metabolic impairment caused by PM2.5. Manufacturing employees, truck drivers and others experiencing long-term daily road traffic should pay close attention to blood markers or liver enzymes that indicate metabolic disease.

“According to our findings, these individuals should adjust their diets and lifestyles to reduce the risk caused by air pollution,” he said.

Dr. Zhang suggests eating a diet high in antioxidants, especially strawberries.

The researchers also recommend that physicians and other health care professionals apply preventive therapeutic strategies or health care approaches toward the liver for patients exposed to regular air pollution.

The study, “Exposure to ambient particulate matter induces a NASH-like phenotype and impairs hepatic glucose metabolism in an animal model,” was published online at www.sciencedirect.com, and is expected to appear in the January issue of the Journal of Hepatology.

In the study, the group exposed an animal model to real-world PM2.5 in Columbus, Ohio, where most of the PM2.5 components were attributed to long-range transport and traffic. In the United States, six of the top 25 cities considered most polluted between 2007 and 2011 were in the Midwest, as reported by the American Lung Association.

“Columbus, where the animals were exposed in this study, is a ‘perfect’ site to study the adverse health effects of PM2.5, and the levels and composition of PM2.5 from Columbus is a regional representative of Midwest source of air pollution in the United States,” Dr. Zhang said.

Recent epidemiologic studies have linked air pollution to the development of type 2 diabetes. Diabetes’ prevalence in the U.S. increased with increasing airborne particulate matter PM2.5 concentrations, as evidenced by a 1 percent increase in diabetes prevalence seen with a 10 μg/m3 (micrograms per cubic meter of air) increase in PM2.5 exposure, he said.

While most researchers in the field are studying the toxic effects of PM2.5 on lung and blood vessels, Dr. Zhang’s team studied the pathological effects and stress mechanisms of PM2.5 exposure on the liver, the organ of detoxification and metabolism closely associated with the development of metabolic disease.

The work revealed that PM2.5 exposure triggers inflammatory stress responses and impairs insulin signaling in the liver, leading to key features of non-alcoholic fatty liver disease, also referred to as non-alcoholic steatohepatitis, or NASH. It affects 2 percent to 5 percent of Americans, according to an April 2012 report of the National Digestive Diseases Information Clearinghouse, a service of the National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, with an additional 10 percent to 20 percent of Americans having fat in their liver with no inflammation or disease.

The project is funded by NIH’s National Environmental Health Science Institute (grant Nos. ES017829, ES016588, ES017412) and National Institute of Diabetes and Digestive and Kidney Diseases (grant No. DK090313).
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