A type of metabolic enzyme, which aids detoxification, has been linked to obesity and fatty liver disease, a new study found.
A team of researchers at the Clemson University found that Cyp2b gene, which metabolizes endo and xenobiotics, may be linked to age-onset obesity and dyslipidemia, especially in males.
Clemson University graduate student Melissa Heintz 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 of Biochemistry, to determine if the exposure to specific chemicals enhances obesity. Specifically, they wanted to identify the role of Cyp2b in unsaturated fatty acid metabolism, regardless of diet. Some chemicals could inhibit the gene, an event shown in the experiment with Cyp2b-null mice.
The team used a laboratory mouse model to explore the role of Cyp2b gene in obesity. It’s an enzyme involved in metabolism, particularly the chemical detoxification in the body. The researchers treated wildtype and Cyp2b-bull mice with a normal or high-fat diet for 10 weeks.
After, they determined the molecular and metabolic changes that happened. They found that the male high-fat-diet-fed Cy2pb-null mice weigh 15 percent more than the wildtype mice given 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 that are metabolized by Cyp2b or inhibitors of Cyp2b, this might mean that you are not metabolizing something else in the body that is important,” William Baldwin, professor and graduate program coordinator in the College of Science’s department of biological sciences, explained.
“In turn, maybe your likelihood of retaining white adipose tissue increases and therefore your likelihood of being obese increases,” he added.
On the contrary, female mice that are Cyp2b-null didn’t manifest increased body weight or white adipose tissue. When the researchers checked the blood samples of the mice, they found increased leptin, cholesterol, and ketosis in male Cyp2b-null mice, compared to wildtype mice.
Furthermore, the liver triglycerides in male Cyp2b-null mice were higher than their counterparts, hinting a role of Cyp2b in fatty acid metabolism, despite having the same diet. Worse, there was a suggestive result of fatty liver disease progression is present in normal diet-fed Cyp2b-null male rats like the one in high-fat diet fed wildtype counterpart. As a result, the researchers found the role of Cyp2b in lipid homeostasis.
This means that the male Cyp2b-null mice had heightened fatty liver disease even with a normal diet.
“Cyp2b must be signaling something and telling the fat to go someplace, indicating that Cyp2b has dual roles: metabolizing toxicants and chemicals in the environment and pharmaceuticals, but it is also involved in the metabolism of lipids and probably involved in signaling to tell us how to distribute fat,” Baldwin added.
“Females did not show as demonstrative changes in liver health, and significantly fewer changes in gene expression, as well as gene expression associated with liver disease,” the researchers said in the study.
“Overall our data indicate that the repression or inhibition of CYP2B may exacerbate metabolic disorders and cause obesity by perturbing fatty acid metabolism, especially in males,” they concluded.
The study is part of a three-year, $362,000 grant the lead author, Baldwin, received from the National Institutes of Health.
Obesity by the numbers
In 2016 alone, there were more than 1.9 billion adults in the world who are overweight. Of these people, more than 650 million had obesity. The global prevalence of obesity almost tripled from 1975 to 2016.
In the United States, 93.3 million adults are obese in 2015 to 2016. Obesity may lead to various complications, some of which are life-threatening. These include type 2 diabetes, some types of cancer, heart disease, and stroke, among others.
The rate of obesity is continuously increasing; hence, studies are focused on finding causative factors that can provide insight into obesity. Also, determining these causes may help in the formulation of treatments and preventive measures to curb the worldwide epidemic.
What is a fatty liver disease?
Nonalcoholic fatty liver disease (NAFLD) is a condition wherein excessive amounts of fat is stored in the liver. The fat buildup is not caused by alcohol intake, instead, it’s linked to being overweight or obese.
Melissa M Heintz, Ramiya Kumar, Meredith M Rutledge, William S. Baldwin, Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in 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)