Metabolic enzyme linked to obesity and hepatic steatosis



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A new study has found that a type of metabolic enzyme facilitating detoxification is linked to obesity and hepatic steatosis.

A team of researchers at Clemson University discovered that the Cyp2b gene, which metabolizes endo and xenobiotics, could be linked to obesity and dyslipidemia, due to aging, especially in men.

Melissa Heintz, a graduate student at Clemson University, and Professor William Baldwin recently published their collaborative research in the Journal of Nutritional Biochemistry. Image Credit: Pete Martin / College of Science

Melissa Heintz, a graduate student at Clemson University, and Professor William Baldwin recently published their collaborative research in the Journal of Nutritional Biochemistry. Image Credit: Pete Martin / College of Science

The researchers conducted the study, which was published in the journal Biochemistry Journal, to determine if exposure to specific chemicals increases obesity. Specifically, they wanted to identify the role of Cyp2b in the metabolism of unsaturated fatty acids, regardless of their diet. Some chemicals could inhibit the gene, an event demonstrated in the experiment with Cyp2b-null mice.

The team used a laboratory mouse model to explore the role of the Cyp2b gene in obesity. It is an enzyme involved in metabolism, especially chemical detoxification in the body. The researchers treated wild-type and Cyp2b-bull mice for 10 weeks with a normal or high-fat diet.

Afterwards, they determined the molecular and metabolic changes that occurred. They found that high-fat diet-fed Cy2pb-null male mice weighed 15% more than wild-type mice fed a high-fat diet. The greater weight has been linked to an increase in white adipose tissue.

There were many potential 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 that is important in the body," said William Baldwin, professor and program coordinator. graduate studies of the Department of Science. biological sciences, explained.

"In return, maybe your chances of retaining white adipose tissue increase and that, as a result, your chances of being obese increase," he added.

In contrast, female mice not containing Cyp2b did not show an increase in body weight or white adipose tissue. When the researchers checked the blood samples from the mice, they found an increase in leptin, cholesterol and ketosis in male Cyp2b-null mice compared to wild-type mice.

In addition, hepatic triglycerides in male Cyp2b-null mice were higher than their counterparts, suggesting a role for Cyp2b in fatty acid metabolism, despite the same diet. Worse still, there was a result suggestive of progression of hepatic steatosis in normal diet-fed male rats fed Cyp2b diet, such as that found in a high fat diet fed to a wild-type counterpart. As a result, researchers discovered the role of Cyp2b in lipid homeostasis.

This means that male Cyp2b-null mice had high fatty liver disease, even with a normal diet.

"Cyp2b should signal something and tell the fat to go away, 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 in signage to tell us how to distribute fat, "Baldwin added.

"Women have not shown any demonstrative changes in liver health, and significantly fewer changes in gene expression, as well as in gene expression badociated with liver disease," they said. said the researchers in the study.

"Overall, our data indicates that repression or inhibition of CYP2B could exacerbate metabolic disorders and cause obesity by disrupting fatty acid metabolism, particularly in men," they concluded.

This study is part of a $ 362,000 grant over three years that the lead author, Baldwin, has received from the National Institutes of Health.

Obesity in numbers

In 2016 alone, more than 1.9 billion adults in the world were overweight. More than 650 million of these people were suffering from obesity. The global prevalence of obesity has almost tripled from 1975 to 2016.

In the United States, 93.3 million adults are obese from 2015 to 2016. Obesity can lead to various complications, some of which are life threatening. These include type 2 diabetes, certain types of cancer, heart disease and stroke, among others.

The rate of obesity is steadily increasing; therefore, studies are focused on finding causal factors that may provide insight into obesity. In addition, the determination of these causes can help in formulating treatments and preventative measures to curb the global epidemic.

What is a fatty liver disease?

NAFLD is a condition in which excessive amounts of fat are stored in the liver. Fat accumulation is not caused by alcohol consumption, it is related to overweight or obesity.

Journal reference:

Melissa M Heintz, Ramiya Kumar, Meredith M Rutledge, William S. Baldwin, Cyp2b-null male mice are susceptible to diet-induced obesity and disturbances of lipid homeostasis, The Journal of Nutritional Biochemistry, https://doi.org/10.1016/. j.jnutbio.2019.05.004. (Http://www.sciencedirect.com/science/article/pii/S0955286318312385)

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