Metabolic enzyme linked to obesity and fatty liver disease

Researchers at the Clemson University Environmental Toxicology Program have published research badociating an enzyme badociated with detoxification, obesity and hepatic steatosis, particularly in men.

William Baldwin, professor and coordinator of postgraduate programs at the Department of Biological Sciences of the College of Science, and members of his lab have used a new mouse model developed in their lab to study the role of the Cyp2b gene in the US. obesity. Cyp2b is a key enzyme involved in metabolism, particularly in the detoxification of chemicals in the body. Among other results, the research indicates a role for Cyp2b in the metabolism of unsaturated fatty acids, regardless of the diet. Some chemicals may inhibit Cyp2b, a phenomenon modeled by Cyp2b-null mice.

The study entitled "Male Cyp2b-null mice are sensitive to diet-induced obesity and disturbances of lipid homeostasis" was published in Diary of nutritional biochemistry. This is part of a $ 362,000 grant, spread over three years, that Baldwin received from the National Institutes of Health to continue his studies on how chemical exposure could inhibit the internal mechanisms of our body. Melissa Heintz, Ramiya Kumar, Meredith Rutledge and Baldwin also participated in the discussion.

"Cyp2b-null male mice are obese – and far more obese – than wild-type mice that are also fed a high-fat diet," Baldwin said.

There are several possible implications for human health.

"If you are exposed to chemicals metabolized by Cyp2b or Cyp2b inhibitors, it may mean that you are not metabolizing anything else important in the body," Baldwin said. "In return, maybe your chances of retaining white adipose tissue increase and that, as a result, your chances of being obese increase."

In addition, male Cyp2b-null mice had an increase in hepatic steatosis without being fed a high fat diet.

"Cyp2b should signal something and tell the fat to disappear, indicating that Cyp2b has a dual role: metabolizing toxic and chemical substances in the environment and pharmaceuticals, but it is also involved in lipid metabolism and probably involved in signaling to tell us how to distribute fat, "said Baldwin.

In the United States, 40% of adults and 18.5% of youth are now considered obese. It is therefore crucial to discover that the enzymes badociated with detoxification can play a role in obesity – beyond the combined effects of diet, exercise and genetics in general.

Female Cyp2b-null mice showed no greater propensity for obesity, although there is some evidence to suggest that they have a higher rate of liver damage than female wild-type mice. .

Gene expression was also affected. Cyp2b-null mice receiving a normal diet have gene expression profiles similar to those of wild-type mice fed a high-fat diet.

"When Cyp2b-null mice receive a regular diet, their liver acts as if they have a high-fat diet," Baldwin said.

Heintz, a third-year PhD candidate in environmental toxicology, said there were still many avenues to explore in this area of ​​research.

"You may be in good health but you may be exposed to a chemical in the workplace," she said. "Even if your diet is good enough, if you lose that activity of an enzyme in your liver, what you might not have thought would be important for fat metabolism."

This discovery also opens the door to the exploration of other enzymes that, at the present time, would have a single role but could also metabolize fats.

"Very little work has been done on this enzyme, Cyp2b, and on its role in the metabolism of fatty acids," said Heintz. "That's just one gene and there could be others who do similar things."

"Despite the obesity, the relative rates of hepatic steatosis were not as high as expected," Baldwin added. "Our study lasted only 10 weeks and if we want to study liver diseases, we have to go further, we have to study the phenomenon of fatty liver, because that's the problem: 25% of the world's population has non-alcoholic fatty liver disease.This increases a bit. "

Kumar has a Ph.D. from Clemson and is now a Senior Clinical Process Associate in a clinical research firm in Bangalore, India. Kumar said future research would show if chemical inhibitors of these genes, such as plasticizers and pesticides, could also induce a similar shift in metabolism and lead to obesity.

"This will help us plan better treatment regimens for obesity, as well as changes in lifestyle and diet," Kumar said.

This research has the potential to inform how scientists are examining a host of metabolic disorders and chronic diseases, all with the goal of improving human health.

"I think it tells us that obesity – and potentially fatty liver disease – is a multi-component disease," Baldwin said. "It's all about eating the wrong foods or eating too much, but external factors can worsen the situation – it's all about chemicals, a lack of nutrition," Exercise or elements of our diet.There are many small pieces to this, and this is a study that indicates that a healthy lifestyle involves a healthy diet, having the right calories and potentially avoiding certain products. chemicals. "

Reference: Heintz et al. 2019. Male Cyp2b-null mice are susceptible to diet-induced obesity and disturbances of lipid homeostasis. Journal of nutritional biochemistry. https://doi.org/10.1016/j.jnutbio.2019.05.004.

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