Comparison of total body, liver and WAT weights between all treatment groups. Total body weight, liver weight, hepatic somatic index (HSI), WAT weight and WAT somatic index (WSI) were measured for all treatment groups. Data are presented as. Statistical significance was determined by one-way ANOVA multiple comparison test with Tukey’s multiple comparison test as the post hoc test (). “a” (age) indicates age difference between young (4.5 months) and old (9 months) mice within the same genotype and diet group, “c” (catch) indicates difference between HFD-fed young (4.5 months) .) and ND-fed old (9 months) mice within the same genotype, “d” (diet) indicates dietary difference between ND-fed and HFD-fed mice within the same genotype and age, and “g” (genotype) indicates genotype difference between WT and Cyp2b -Zero mice within the same diet and age group. No star indicates a value Journal of Lipids (2022). DOI: 10.1155 / 2022/7122738
A team of researchers from Clemson University delves into the understanding of the relationship between certain enzymes normally produced in the body and their role in regulating obesity and controlling liver disease.
According to data from the Centers for Disease Control and Prevention (CDC) collected in 2017-18, more than 42% of U.S. adults and 19% of U.S. adolescents are overweight.
Three Clemson researchers and colleagues from Emory University School of Medicine studied male mice lacking the Cyp2b enzyme and how the deficiency of the enzyme affected the mice’s metabolism.
William Baldwin, professor and master’s program coordinator in Clemson’s Department of Biological Sciences, said the research was triggered in part by a simple observation: male mice lacking the Cyp2b enzyme took on. The same effect was not observed in female Cyp2b-null mice.
“We noticed that our Cyp2b-zero mice were heavier,” said Baldwin, a professor in the Department of Biological Sciences. “They are more prone to obesity – at least diet-induced obesity – especially in males than wild-type mice, and we were trying to figure out why that is.”
While the observation that tipped the researchers was quite straightforward, it turned out that the understanding of the interactions behind the 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.”
Baldwin noted the complexity of several chemical processes involving the CYP enzyme, part of a superfamily of enzymes that play a variety of roles in humans. He said Cyp2b enzymes help metabolize certain toxins and drugs 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. “That means all of these things can also interact. If you have a diet that is full of fat, it can inhibit your metabolism. Of course … medication can inhibit your fat metabolism, can affect your steroid metabolism, and so on.”
The researchers also looked at the link between “disturbed lipid profiles” and disease.
Disease susceptibility and overall health are strongly affected by changes in the lipidoma, the researchers noted. Fatty diets, such as the Western diet, cause obesity and drastically alter hepatic lipidoma, and disturbed lipid profiles are associated with specific liver diseases, such as non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).
Credit: Clemson University
Influence of age and diet
Baldwin has led earlier research into the relationship between diet and environmental toxins. The most recent study focused on the impact of age and diet on these metabolic processes.
“What does a bad diet do to us? What does age do to us? That’s the idea here,” Baldwin said of the latest research. “We’re looking at these enzymes; what can happen over time with our profiles in this mouse model compared to just a wild-type mouse. What can happen over time with a high-fat diet, what can happen as we get older, and how does it differ between this one mouse model that does not have these enzymes compared to one that has these enzymes. “
In short, Baldwin said, “One of the things we saw, and not surprisingly, is that it’s bad to get older. It’s harder for mice to regulate their body weight. They gain weight. The weight they have is more white adipose tissue. [connective tissue mainly comprising fat cells]. … And some of these things were a little bit worse in the mice that lacked Cyp2b enzymes. They were a little heavier. They had a little more fat than their peers. Their liver was a little bit bigger and a little bit less healthy. So they had a lot of the things that we associate with age that go on. “
The 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: eating a bad diet caused weight gain, and it was a little worse with these [Cyp2b-null] mice, probably due to poor metabolism. “
He said the exact mechanism by which the Cyp2b enzyme works is not fully understood.
“You remove an enzyme that helps metabolize these, but I do not think it’s really important that it helps get rid of the fat, but that it lets the body know that the fat is there. It probably produces signaling molecules, who says ‘hey, we have to decide what to do with this fat, we have to distribute this fat.’ That kind of information. It’s just a qualified guess at the moment, but I think that’s 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 research, which will be part of an as yet unpublished paper, indicates that the mouse and the human enzymes are unlikely to work exactly the same. “The human enzyme seems to cause us to retain some of the fat in the liver, and the mouse enzyme seems to drive it to the white adipose tissue. There are hints here in this paper that this is the case,” Baldwin said.
The results of the study were published in the Journal of Lipids in a paper entitled “Age- and diet-dependent changes in hepatic lipidomic profiles of phospholipids in male mice: age acceleration in Cyp2b-Zero mice.”
Researchers link metabolic enzyme to obesity and fatty liver disease More information: Melissa M. Heintz et al., Age- and Diet-Dependent Changes in Hepatic Lipidomic Profiles of Phospholipids in Male Mice: Age Acceleration in Cyp2b-Null Mice, Journal of Lipids (2022) ). DOI: 10.1155 / 2022/7122738
Quote: Researchers Study Relationships Between Obesity, Age And Body Chemistry (2022, May 11) Retrieved May 13, 2022 from https://medicalxpress.com/news/2022-05-scientists-links-obesity-age-body.html
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