Nonalcoholic fatty liver disease (NAFLD) is escalating in California and the United States and is associated with the rising obesity epidemic. NAFLD is a hepatic phenotype that encompasses the more serious manifestation of steatohepatitis (NASH), considered to be a prerequisite for liver cancer (hepatocellular carcinoma/HCC). We also know from recent clinical studies that chemical toxicant exposure, in the absence of obesity, can lead to toxicant-associated steatohepatitis (TASH), which closely resembles the pathology of NASH. These findings are relevant to SRP stakeholders in Region 9, since California ranks high in National Priorities List (Superfund sites) nationally and contains thousands of additional hazardous waste sites (HWS). In addition, the UCSD NAFLD Research Center shows that American Indians and Hispanics, combined the largest non-Caucasian population in California, are at far greater risk of developing NAFLD. Over the past five years, our SRC has leveraged resources to demonstrate that TASH is greatly accelerated by consumption of high-fat diet (HFD) or after a diabetic episode in mice. These findings are relevant, since we can speculate that American Indians and Hispanics are more susceptible to TASH development, a risk amplified by unhealthy diets, poverty and health disparities. The UCSD SRC will be developing models through its Biomedical projects to characterize the mechanisms of Superfund toxicant induced TASH development and cancer, while the Environmental Science & Engineering (ES&E) projects will develop tools for NPL-toxicant detection and remediation. Biomedical and ES&E projects will be assisted in these efforts by Research Core services that will provide tools for mouse genetic production, metabolomic and sophisticated Bioinformatic analysis. A key objective of the projects is to highlight scientific findings to maximize Research Translation, which will happen with collaborations between the projects and the Research Translation Core. We believe our program is innovative and paradigm shifting, since it has the potential of linking important basic research findings regarding Superfund toxicant exposure with human disease biomarker identification through collaborations with the UCSD NAFLD Research Center, which contains one of the largest NALFD cohort studies in the world. Importantly, our Biomedical findings and tools developed in the ES&E projects will be used as resources and knowledge gained to reduce cumulative impacts and health disparities. These initiatives will be leveraged through Community Engagement Core efforts in disadvantaged Hispanic neighborhoods in San Diego and Mexico where statistics confirms that obesity is an escalating problem both in children and adults. Since the incidence of NAFLD and liver cirrhosis is on the rise in both children and adults and may be linked to toxicant chemical exposure, our findings will be communicated to SRP primary stakeholders at the U.S. Environmental Protection Agency and the Agency for Toxic Substances and Disease Registry, in addition to state and local agencies.

Public Health Relevance

Center Narrative Of key importance to the Superfund Research Program (SRP) and SRP?s primary stakeholders is the link between nutrition, health disparities and environmental toxicant exposure toward the development of fatty liver disease, steatohepatitis, cirrhosis and liver cancer. Work conducted at the UCSD SRP Center is dedicated towards understanding the mechanisms associated with toxicant-induced steatohepatitis (TASH) and cancer, which may be an escalating problem in many susceptible Hispanic and American Indian communities that are exposed to household, occupational and industrial chemical exposure. Our efforts will provide important findings linking mechanisms of TASH and cancer with disease prognosis, which can be communicated to impacted communities to serve as intervention tools to assist in prevention of toxicant exposure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
5P42ES010337-19
Application #
9903330
Study Section
Special Emphasis Panel (ZES1)
Program Officer
Heacock, Michelle
Project Start
2000-07-01
Project End
2022-03-31
Budget Start
2020-04-01
Budget End
2021-03-31
Support Year
19
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Pharmacology
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
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