A team of scientists at Clemson University has discovered that CYP2B — a key enzyme involved in metabolism, particularly in the detoxification of chemicals in the body — plays a role in obesity and fatty liver disease, especially in males.
“Our research indicates a role for Cyp2b in unsaturated fatty acid metabolism, regardless of diet,” Professor Baldwin said.
“Certain chemicals could inhibit Cyp2b, a phenomenon modeled by Cyp2b-null mice.”
“The male Cyp2b-null mice are obese — and much more obese — than the wild-type mice that are also fed a high fat diet.
There are several possible implications to 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,” Professor Baldwin said.
“In turn, maybe your likelihood of retaining white adipose tissue increases and therefore your likelihood of being obese increases.”
In addition, male Cyp2b-null mice had increased fatty liver disease without being fed a high-fat 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 metabolism of lipids and probably involved in signaling to tell us how to distribute fat,” he said.
Female Cyp2b-null mice did not show any greater propensity toward obesity, though there were indications that they have a higher rate of liver damage than wild-type female mice.
Gene expression was also affected. Cyp2b-null mice fed a normal diet have gene expression profiles similar to wild-type mice fed a high-fat diet.
“When the Cyp2b-null mice are fed a regular diet, their livers are acting like they are being fed a high fat diet,” Professor Baldwin noted.
“There are still many pathways to explore in this area of research,” said Melissa Heintz, first author of the study.
“You might be healthy but you might be exposing yourself to a chemical in the workplace. Even though your diet is pretty good, if you are losing this activity of an enzyme in your liver, what you may not have thought would be important may be important in metabolizing fat.”
The results were published in the Journal of Nutritional Biochemistry.
Melissa M. Heintz et al. 2019. Cyp2b-null male mice are susceptible to diet-induced obesity and perturbations in lipid homeostasis. Journal of Nutritional Biochemistry 70: 125-137; doi: 10.1016/j.jnutbio.2019.05.004