The latest study by the Nobel Prize winner team: "Drinking water is fat" turns out to be a defect in this gene

Dr.
Zhao Zhang

The findings, published in the journal Cell Metabolism, describe how a genetic defect called Ovol2 causes mice with normal activity levels and food intake to become obese in adulthood due to problems with body heat
.
If the same happens in humans, who share nearly the same genes and their protein products, the discovery could eventually help identify potential obesity treatments
.

"Most cases of obesity are caused by overeating or lack of physical activity, but our study shows that mutations in a rarely studied gene called Ovol2 cause massive obesity, which is entirely due to defects in thermogenesis or thermogenesis," said study leader Dr.
Zhao, assistant professor of internal medicine who co-led the study
with Nobel laureate, professor of immunology and director of the Center for Host Defense Genetics, M.
D.

Bruce Beutler, M.
D

About 42 percent of Americans are obese, a condition that increases the risk of many other health problems, including heart disease, stroke, type 2 diabetes and certain types of cancer
.
Although researchers agree that obesity appears to stem from an interaction between a person's genes and the environment in which he or she finds itself, genes that play an important role in the most common forms of obesity are not well known, and the most well-known obesity mutation in mice and humans causes appetite extension
.

To learn more about the basic mechanism of obesity, Beutler and their colleagues used a chemical to create random mutations
in the DNA of mice.
In one particular family of mice, obesity began at about 10 weeks of age — a young adult for these rodents — and continued until the animals were severely overweight
.
The researchers found the responsible mutation
in a gene called Ovol2.

"No one has previously linked this gene to obesity," says Dr.
Beutler, "because it's essential
for life.
" The mutations we created were mild enough to survive, but also destructive enough to expose staggering metabolic defects
.
”

Compared to normal brown fat (left), Ovol2 mutant brown fat (right) has defects in thermogenesis and has a large amount of additional lipid accumulation (large white hole).

Compared to non-littermate mice, obese mice had a 556 percent increase in fat weight and a 20 percent
reduction in lean mass.
Experiments have shown that obese animals are unable to maintain core body temperature when exposed to cold, seemingly due to their inability to effectively use a tissue called brown fat, whose main function is to generate heat
.
Further testing showed that the healthy Ovol2 gene inhibited the development of white fat, the main tissue
responsible for energy storage.

When the researchers overexpressed the normal Ovol2 protein, they found that the animals gained much less weight than the wild-type control group
in mice fed a high-fat diet.
The authors say the findings suggest that Ovol2 plays a key role in energy metabolism — which may be true in humans, where the Ovol2 protein is very similar
to that of mice.
Doctors may eventually treat obesity
by giving patients drugs that improve Ovol2 function.