In mice without the enzyme, however, the males developed some fat but females remained lean, and this occurred even when females ate more food than males. The researchers determined that without Aldh1a1, the females were not producing retinoic acid, and that protected them from producing visceral fat. Meanwhile, males retained the ability to produce retinoic acid.
The scientists then analyzed the proteins contained in fat tissue in male and female mice lacking the enzyme, and saw that only the females' fat cells contained high levels of a protein that releases fat from fat cells to support fat burning. This release led to production of another protein that converts fat to heat, essentially burning the fat, in the form of lipids, away.
"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," Ziouzenkova said. "And this process was specifically affecting visceral fat."
The researchers surgically removed the ovaries of mice to test whether estrogen could be related to visceral fat production in females. As soon as the animals became menopausal and weren't producing estrogen, they began to produce retinoic acid, which led to visceral fat formation.
"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," said Ziouzenkova, also an investigator in Ohio State's Comprehensive Cancer Center.
Using another mouse model that allowed researchers to measure hormone production specifically, the researchers observed that female mice on a regular diet barely produced retinoic acid. However, females on a high-fat diet produced high levels of the hormone and, in turn, showed a n
|Contact: Ouliana Ziouzenkova|
Ohio State University