Researchers link metabolic enzyme to obesity, fatty liver disease

A metabolic enzyme appears to be associated with detoxification to obesity and fatty liver disease, according to new research from Clemson University in South Carolina, and published in the Journal of Nutritional Biochemistry.

The research team, led by William Baldwin, PhD, professor and graduate program coordinator in the department of biological sciences, used a mouse model developed in their laboratory to study the role of the Cyp2b gene in 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 unsaturated fatty acid metabolism, regardless of diet. Certain chemicals could inhibit Cyp2b, a phenomenon modeled by Cyp2b-null mice, researchers said.

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

With 40 percent of adults and 18.5 percent of youth in the United States now considered obese, the discovery that enzymes associated with detoxification may play a role in obesity, beyond the compounding effects of diet, exercise and general genetics, is critical, researchers said.

This research has the potential to inform how scientists look at a host of metabolic disorders and chronic conditions, all with the goal of increasing human health.

"I think it tells us that obesity, and potentially fatty liver disease, is a multi-component disease," said Baldwin. "It is about, first and foremost, eating the wrong foods or eating too much. But we can make it worse by external factors, whether that's chemicals, a lack of exercise or the components of our diets. There are a lot of little pieces to that, and this is one study that indicates that a healthy lifestyle involves a healthy diet, having the right calories and potentially avoiding some chemicals as well."