Scientists are studying the links between obesity, age and body chemistry.
Obesity is described as the abnormal or excessive accumulation of fat that is a health problem. This condition has become widespread in the United States. According to statistics collected by the Centers for Disease Control and Prevention (CDC) in 2017-18, more than 42 percent of US adults and 19 percent of US youth are obese.
Unfortunately, obesity rates among adults and children continue to rise. From 1975 to 2016, the global prevalence of overweight or obese children and adolescents aged 5–19 more than quadrupled, from 4% to 18%. It’s widely believed that obesity is caused by overeating and not exercising enough, but recent studies suggest other factors may play a role.
A Clemson University research team is making progress in understanding the connection between certain enzymes naturally produced in the body and their role in treating obesity and controlling liver disease.
Three Clemson researchers and colleagues from Emory University School of Medicine analyzed male mice lacking the Cyp2b enzyme and how the lack of the enzyme affected the mice’s metabolism.
According to William Baldwin, a professor and graduate program supervisor at the Clemson Department of Biological Sciences, the study was prompted in part by a simple observation: Male mice lacking the Cyp2b enzyme gained weight. Female Cyp2b null mice did not show the same effect.
“We found that our Cyp2b null mice were heavier,” said Baldwin, a professor in the Department of Life Sciences. “They are more prone to obesity — at least diet-related obesity — particularly in males than wild-type mice, and we’ve been trying to figure out why that is.”
While the observation that gave the researchers the tip was fairly simple, it turned out that understanding the interactions behind weight gain would be much more complex.
“It would be nice if there was a nice, simple answer,” Baldwin said, “but there probably isn’t a nice, simple answer.”
variety of roles
Baldwin pointed out the complexity of several chemical processes involving the CYP enzyme, which is part of an enzyme superfamily that performs a variety of functions in humans. According to him, the Cyp2b enzymes help metabolize certain toxins and drugs in order to remove them from the body.
But the same CYP enzymes also have other jobs. “They metabolize bile acids; they metabolize steroid hormones; they metabolize polyunsaturated fats from our diet,” Baldwin said. “It means that all of these things can also interact. If you have a high-fat diet, it can inhibit your drug metabolism. Of course … drugs can inhibit your fat metabolism, affect your steroid metabolism and so on.”
Researchers also looked at the link between “disturbed lipid profiles” and disease.
Disease susceptibility and overall health are strongly influenced by changes in the lipidome, the researchers found. High-fat diets such as the Western diet cause obesity and drastically alter the hepatic lipidome, and abnormal lipid profiles are associated with certain liver diseases such as nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH).
Influence of age and diet
Baldwin has previously led research examining the link between diet and environmental toxins. The most recent study looked at how aging and diet affect these metabolic processes.
“What does poor nutrition do to us? What is age doing to us? That’s kind of an idea here,” Baldwin said of the latest research. “We look at these enzymes; what might happen over time with our profiles in this mouse model compared to a pure wild-type mouse. What might happen over time on a high-fat diet, what might happen as we age, and how does this one mouse model that doesn’t have these enzymes differ from one that does.”
Put simply, Baldwin said, “One of the things that we’ve seen, and not surprisingly, is that aging is bad. It is more difficult for the mice to regulate body weight. You gain weight. The weight they have is more white adipose tissue [connective tissue mainly comprising fat cells]. … And some of those things were a little worse in the mice that lacked the Cyp2b enzymes. They were a little heavier. They had slightly more fat than their peers. Their livers were a little bigger and a little less healthy. So they had a lot of those things that we associate with aging.”
Diet also had an impact on the health of the mice.
“Of course, the diet didn’t help either,” Baldwin continued. “It’s the same case: poor diet caused weight gain, and these were a little worse [Cyp2b-null] Mice, probably because of poor metabolism.”
He said the exact mechanism by which the Cyp2b enzyme works is not yet fully understood.
“You’re taking away an enzyme that helps metabolize them, but I don’t think it’s really important that it helps get rid of the fat, it’s just letting the body know the fat is there. It probably produces signaling molecules that say, “Hey, we need to decide what to do with this fat; we have to spread this fat.” That kind of information. That’s just an educated guess at this point, but I think that’s likely what’s happening.
differences in humans
Baldwin said his current research takes a closer look at the mechanisms at play and how they differ in a human model from the mouse studies.
He said the research, which will be part of a yet-to-be-published paper, suggests the mouse and human enzymes probably don’t work the same way. “The human enzyme seems to cause us to keep some of the fat in the liver, and the mouse enzyme seems to drive it into the white adipose tissue. There is evidence here in this paper that this is the case,” Baldwin said.
A grant from the National Institutes of Health supported the research.
Reference: “Age- and Diet-Dependent Changes in Hepatic Lipidome Profiles of Phospholipids in Male Mice: Acceleration of Age in Cyp2b-Null Mice” by Melissa M. Heintz, Ramiya Kumar, Kristal M. Maner-Smith, Eric A. Ortlund, and William S. Baldwin , March 29, 2022, Journal of Lipids.