Toxic fats, vitamin B12 loss, and AHR may drive fatty liver disease
Official title: Toxic lipid intermediate accumulation and cobalamin depletion promote AHR-mediated hepatotoxicity and the progression of non-alcoholic fatty liver disease (NAFLD)-like pathologies
Funded at Michigan State University · NIH-11398883 · Data updated 2026-11-12
This grant looks at how certain environmental chemicals may trigger liver damage linked to fatty liver disease and how a vitamin found in the blood could be affected.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Michigan State University NIH-funded |
| Lab location | 1 site (East Lansing, United States) |
| Project start | September 1, 2025 |
| Project end | August 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $569,905 |
| NIH project number | 5R01ES033898-03 |
| Project ID | NIH-11398883 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates include individuals with NAFLD or metabolic liver concerns who have environmental exposure histories or related biomarkers.
✕Less likely to help
People without NAFLD or exposure-related liver risk may not benefit from this study’s findings.
What this research studies
The project focuses on how exposure to toxins like TCDD activates a receptor that changes liver fat metabolism and may push simple fatty liver toward more serious liver disease. Researchers will combine RNA and metabolite data to understand how these toxins disrupt fat breakdown, bile acids, and vitamin B12 levels in the liver. They aim to identify the sequence of events that leads to hepatotoxicity and NAFLD-like pathologies in a mouse/human-relevant context. The study could uncover targets for preventing toxin-related liver injury in people with fatty liver disease or at risk due to environmental exposures.
Why it matters
Potential benefit: If successful, the research could reveal ways to prevent or slow toxin-driven liver damage in people with NAFLD.
How similar studies have gone: Prior work shows environmental toxins can worsen fatty liver disease, suggesting a plausible path toward translation, though human-specific outcomes remain to be confirmed.
Where this research is happening
-
Michigan State University
East Lansing, United States Active
Researchers
- Principal investigator: Zacharewski, Timothy R. — Michigan State University
- Study coordinator: Zacharewski, Timothy R.
Related research
Other NIH-funded projects on the same topics.
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NAFLD in PCOS: Do androgens drive liver injury and fatty liver progression?
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Better liver imaging for nonalcoholic fatty liver disease
This research is creating new MRI techniques to check for liver inflammation and damage in people with nonalcoholic fatty liver disease without needing a biopsy.
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How Androgens Affect Liver Health in Women with PCOS
This project explores how elevated androgen levels in women with Polycystic Ovary Syndrome (PCOS) may lead to liver damage and the progression of fatty liver disease.
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The impact of androgens on liver health in women with Polycystic Ovary Syndrome.
This study is looking at how high levels of certain hormones in women with PCOS might harm their liver and lead to fatty liver disease, and it hopes to find ways to help improve liver health for those affected.
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Investigating how toxic lipids and vitamin B12 depletion affect liver disease progression.
This study is looking at how a chemical called TCDD from the environment might make non-alcoholic fatty liver disease worse, and it hopes to find out how this happens so that people with liver issues can better understand what affects their health.
-
Role of fat droplets in liver fat and inflammatory signals in NAFLD
A study at Johns Hopkins will explore how fat droplets in the liver influence molecules that drive inflammation and progression of non-alcoholic fatty liver disease (NAFLD) in adults.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.