Environmental Factor – April 2022: Environmental exposures underpin many metabolic diseases, expert says

When NIEHS grantee Lida Chatzi, MD, Ph.D., ran a pediatric obesity clinic in Crete, Greece more than a decade ago, she was struck by the daunting complexity of metabolic diseases.

Chatzi, a physician environmental epidemiologist, is deputy director of the NIEHS-funded Southern California Environmental Health Sciences Center at USC. She is also the principal investigator for the Rhea Mother-Child Study in Greece, and she has had significant leadership roles in large cohort studies investigating environmental exposure early in life. (Photo courtesy of Andrew Zaw/USC)

“Since the beginning of my career, it has been clear to me that you cannot simply follow a specific diet or run for 30 minutes a day to solve the problem of obesity,” she said. “It’s more complicated than that.”

Today, Chatzi has established a research program to understand how exposure to environmental chemicals affects metabolic diseases such as obesity, diabetes, non-alcoholic fatty liver disease, and cancer. She is a professor of Population and Public Health Sciences at the University of Southern California (USC) and directs the school’s Center for Translational Research on Environmental Health.

Chatzi recently led an international research team to identify metabolic “signatures” that can determine nutrition quality in children and predict their metabolic health. The study, published in the journal eLife, is one of several projects integrating human population data and new laboratory methods to provide important insights into exposure risk and disease development.

Health in crisis

According to Chatzi, Americans’ health has been declining for decades. This decline has been linked to the rising incidence of chronic diseases such as obesity and heart disease in certain regions of the US

“The epidemic of many of these metabolic diseases follows the same geographic pattern,” she said. “Genetics can’t explain these kinds of trends, so we need to focus on the environment.”

Her research focuses on a relatively new scientific concept called the exposome, which aims to capture not just a single environmental exposure, but the aggregate of exposures a person experiences during his or her lifetime. Chatzi’s lab uses advanced ‘omics technologies — such as exosomics, proteomics and metabolomics — to investigate how the environment affects human health.

Early life exposures

For example, Chatzi and her colleagues showed that exposure in utero to a mixture of so-called forever chemicals known as PFAS, or per- and polyfluoroalkyl substances, can increase the risk of liver damage in children. They found similar effects after prenatal exposure to high levels of mercury.

Interestingly, her team found that children whose mothers ate the recommended one to three servings per week of fish — which are often contaminated with mercury but are also a source of important nutrients — had better metabolic health than children whose mothers rarely fish. at.

A natural experiment

More recently, Chatzi has begun exploring the use of bariatric surgery as a “natural experiment” to study the metabolic effects of environmental exposure. She found that some participants in the Teen-LABS (Longitudinal Assessment of Bariatric Surgery) study lost and maintained weight after surgery, while others quickly regained it. The difference in outcomes cannot be explained simply by diet or physical activity.

“Our hypothesis is that environmental pollution, the chemicals stored in body fat, may explain some of the variability,” Chatzi said. Her latest grant from NIEHS allows her to test this hypothesis.

The influence of nutrition

Another hypothesis Chatzi is investigating is whether diet can be an important factor in offsetting the impact of the environment on metabolic diseases.

For example, some studies have shown that the effect of air pollution on cardiovascular disease can be buffered by a Mediterranean diet, which is rich in antioxidants.

Human-relevant explanations

Last October, Chatzi announced the launch of the USC Center for Translational Research on Environmental Health, which she leads (Learn more in this Environmental Factor article.)

She noted that the center aims to increase knowledge about how the exposome affects metabolic disease.

Chatzi added that through innovative research designs and interdisciplinary approaches, scientists will advance understanding of how a variety of environmental exposures can affect our biology.

“Our goal is to drive the translation of basic biomedical and environmental health research into concrete strategies that protect and improve human health,” she said.

Stratakis N, Siskos AP, Papadopoulou E, Nguyen AN, Zhao Y, Margetaki K, Lau CE, Coen M, Maitre L, Fernandez-Barres S, Agier L, Andrusaityte S, Basagana X, Brantsaeter AL, Casas M, Fossati S, Grazuleviciene R, Heude B, McEachan RRC, Meltzer HM, Millett C, Rauber F, Robinson O, Roumeliotaki T, Borras E, Sabido E, Urquiza J, Vafeiadi M, Vineis P, Voortman T, Wright J, Conti DV, Freedom M , Keun HC, Chatzi L. 2022. Urine metabolic biomarkers of dietary quality in European children are associated with metabolic health. eLife; doi:10.7554/eLife.71332 [Online 25 January 2022]†

Stratakis N, Golden-Mason L, Margetaki K, Zhao Y, Valvi D, Garcia E, Maitre L, Andrusaityte S, Basagana X, Borras E, Bustamante M, Casas M, Fossati S, Grazuleviciene R, Haug LS, Heude B, McEachan RRC, Meltzer HM, Papadopoulou E, Roumeliotaki T, Robinson O, Sabido E, Urquiza J, Vafeiadi M, Varo N, Wright J, Vos MB, Hu H, Freedom M, Berhane KT, Conti DV, McConnell R, Rosen HR , Chatzi L. 2021. In utero exposure to mercury in childhood is associated with increased susceptibility to liver damage and inflammation. Hepatology 74(3): 1546-1559.

Stratakis N, Conti DV, Borras E, Sabido E, Roumeliotaki T, Papadopoulou E, Agier L, Basagana X, Bustamante M, Casas M, Farzan SF, Fossati S, Gonzalez JR, Grazuleviciene R, Heude B, Maitre L, McEachan RRC , Theologidis I, Urquiza J, Vafeiadi M, West J, Wright J, McConnell R, Brantsaeter A, Meltzer HM, Freedom M, Chatzi L. 2020. Association of fish consumption and mercury exposure during pregnancy with metabolic health and inflammatory biomarkers in children . JAMA Netw Open 3(3):e201007.

Stratakis N, Conti DV, Jin R, Margetaki K, Valvi D, Siskos AP, Maitre L, Garcia E, Varo N, Zhao Y, Roumeliotaki T, Vafeiadi M, Urquiza J, Fernandez-Barres S, Heude B, Basagana X, Casas M, Fossati S, Grazuleviciene R, Andrusaityte S, Uppal K, McEachan RRC, Papadopoulou E, Robinson O, Haug LS, Wright J, Vos MB, Keun HC, Freedom M, Berhane KT, McConnell R, Chatzi L. 2020. Prenatal exposure to perfluoroalkyl substances associated with increased susceptibility to liver injury in children. Hepatology 72(5): 1758-1770.

(Marla Broadfoot, Ph.D., is a contract writer for the NIEHS Office of Communications and Public Liaison.)

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