U.S. Department of Energy

Pacific Northwest National Laboratory

High-Fat Diets Alter Metabolism, Resulting in Susceptibilities to Common Exposures

A high-fat diet (HFD) is a common exposure that results in obesity and associated pathologies including hepatotoxicity.

Study investigates a common human exposure coupled with a high-fat diet. 

The Science                      

A study led by Aaron Wright of Pacific National Laboratory determined that high-fat diets lead to dramatic alterations in liver and lung metabolism, which significantly changes the body’s response to common chemical and environmental exposures.  

The rate of obesity has doubled since 1980, thanks to high-fat diets. Regular consumption of fatty foods leads to chronic inflammation, metabolic diseases, and increased likelihood for a wide range of co-morbidities. Despite this evidence, little is known about how key metabolic enzymes in the liver and lungs respond to high-fat diets. 

The study reveals that metabolic changes can be drastic as a result of consuming fatty foods, which can lead to critical susceptibilities. For example, the body may not be able to properly process nutrients or pharmaceutical drugs.  

The Impact

By defining the impacts on metabolic activities by obesity related to high-fat diets, the study enhances our understanding of susceptibilities to associated health risks and suggests new avenues for improved  therapeutic practices, including dosing levels. 


Obesity as a result of high-fat diets is rapidly becoming a worldwide epidemic, along with that epidemic comes a host of metabolic complications and chronic diseases. The research team hypothesized that obesity may also severely complicate metabolic activities in the lung and liver that are critical to detoxification of common exposures ranging from cigarette smoke to pharmaceuticals.  

Using an activity-based protein profiling technique, the team characterized and quantified functionally active metabolic enzymes in the liver and lung. The results indicated that mice fed high-fat diets had significantly decreased enzyme activity, likely instigated by proinflammatory chemicals, and that  enzymes involved in detoxification, xenobiotic metabolism, and bile acid synthesis were negatively) affected. This research paves the way to understanding how diet-induced obesity must be accounted for in critical metabolic pathways in order to enhance human health. That includes suggesting ways to improve the safety and efficacy of therapeutic drug dosing.


Sadler NC, Webb-Robertson B-J, Clauss TR, Pounds JG, Corley RA and Wright AT. “High-fat diets alter the modulatory effects of xenobiotics on cytochrome P450 activities.”Chem. Res. Toxicol.2018. PMID: 29688711.

June 2018
| Pacific Northwest National Laboratory