The experts explained a process in female mice which begins with an enzyme being activated and ending when visceral fat forms. This type of fat builds up around internal organs and is associated with an increased risk of cancer, type 2 diabetes and heart disease.
Although the enzyme performs many tasks, one involves producing a strong hormone which pushes the visceral fat cells to form. Vitamin A is the main source for this hormone.
When both men and women eat a high fat diet, the levels of this enzyme are higher in the women. After the experts altered the genetics of the mice by taking away the enzyme, the females remained slender, specifically, in their stomachs, even when they continued high fat diets. The scientists noticed a drop in fat in the males as well, however, the difference was not as dramatic as in the females.
This enzyme could eventually be targeted for either male or female obesity treatment.
Ouliana Ziouzenkova, senior author of the study, and an assistant professor of human nutrition at Ohio State University explained:
"If you asked most people what they believe causes obesity, they would probably say high food consumption and a sedentary lifestyle. But we see that there are genetic factors telling the body what to do with fat. A high-fat diet acts on our genetics to make us more fat or less fat. The diet is not powerful enough to do this on its own."
Additional trials found that fat cells in female mice which don't contain the enzyme may manufacture proteins which obtain their heat from fat. This means that the fat in the female mice was burns away.
Fat tissue from humans who had undergone surgery was examined by the experts and they found that the enzyme also exists in humans. The levels in the cells taken from the visceral fat of overweight women were much higher than the ones removed from thin women.
The trial also revealed that estrogen stops the enzymes from working. This may explain why women sometimes store fat in their stomachs after menopause.
The hormone effects in mice were similar to how women process vitamin A, which is a nutrient that can be transformed into many different compounds. These involve a molecule which assists in producing energy by burning fat, and also retinoic acid - the hormone involved in this trial which aids the making of visceral fat.
According to the researchers, high-fat diets work as a "switching mechanism" by separating the molecule that burns fat, which jump starts the enzyme and the making of retinoic acid, eventually resulting in visceral fat development ending. Last year, Ziouzenkova and her colleagues discovered an enzyme which is involved in the build up of fat, called Aldehyde Dehydrogenase 1 (aldh1a1). The new study involved multiple investigations in mice to determine the process after the enzyme is triggered.
Normal and genetically altered mice that did not possess the enzyme were compared by the authors after a year of living on a high-fat diet. The normal mice, both male and female, naturally gained excess weight. However, the females had more visceral fat around their organs than the males, which also has been seen in humans after eating too much fat.
On the other hand, on normal diets, men are more likely to develop fat in the abdominal region than women. The female and male mice both showed increased peripheral subcutaneous fat, the fat found directly under the skin which can provide advantages.
The female mice that had been genetically altered to not have the enzyme stayed thin, while the males formed some fat. This remained the same, even when the females ate more than the females.
The experts found that when Aldh1a1 was taken from the females, they stopped making retinoic acid, which resulted in protection from making visceral fat. Unlike the females, the males were still able to manufacture retinoic acid.
After they came to these conclusions, the scientists explored the proteins from the fat tissue of the mice with no enzymes. They discovered that the females' fat cells had high levels of a protein responsible for letting fat escape from fat cells, which assists in the burning of fat. When the fat is released, another protein is formed which aids in the fat to heat conversion, resulting in the burning of fat as lipids. Ziouzenkova commented: "Without production of the hormone retinoic acid, females are burning fat and expending the energy in the form of heat. That's why they stay very lean. And this process was specifically affecting visceral fat."
To determine if estrogen was associated with the making of visceral fat in females, the scientists removed their ovaries. When the mice transitioned into menopause and stopped making estrogen, the started to create retinoic acid, eventually resulting in the development of visceral fat.
Ziouzenkova, who also works as an investigator at Ohio State's Comprehensive Cancer Center, explained:
"Estrogen was sufficient to protect female mice from both hormonal and, partially, diet-induced obesity. This means estrogen is suppressing activation of the obesity-inducing hormone, and as soon as we lose this estrogen during menopause, the visceral fat starts to grow."
In another phase of the study, the researchers used a different mouse model which made it possible to solely measure hormone production. They found that female mice on normal diets scarcely made retinoic acid, but the ones one a high-fat diet showed high levels of the hormone, which resulted in a nine-fold increase of visceral fat when compared with that of the male mice on high-fat diets. This solidified the fact that there is a link between visceral fat formation and high-fat diets.
Ziouxenkova says of the human fat tissue samples that because they showed high levels of Aldh1a1 in the cells taken from overweight women, "it could be that what we show about this hormone's importance to visceral obesity in mice is also true for humans.
"As soon as a female starts the high-fat diet consumption, a mechanism for hormonal regulation is turned on and she starts to produce retinoic acid and her metabolism becomes super thrifty. Females will store more fat than they burn. By removing the Aldh1a1 enzyme in visceral fat, we could make females release fat and burn it. We make them super-metabolically active instead."
Written by Christine Kearney