Silencing of ER-alpha expression in mice caused increases in visceral fat and impairment of glucose tolerance.

University of Cincinnati Academic Health Center researchers say that they have new evidence of how menopause could account for the increase in appetite and accompanying weight gain that often occurs among aging women.

In a series of animal experiments, the researchers showed that estrogen receptors located in the hypothalamus serve as a master switch to control food intake, energy expenditure, and body fat distribution. When these receptors are destroyed, the animals immediately begin to eat more food, burn less energy, and pack on pounds.

Previous studies have shown that estrogen receptor alpha (ER-alpha) plays a role in regulating food intake and energy expenditure.

To determine the effect of dwindling estrogen levels in the brain, the scientists focused on an ER-alpha rich region located in the hypothalamus. The region, called the ventromedial nucleus (VMN), is a center for energy regulation. The investigators deactivated the alpha-receptors in the VMN of mice using RNAi.

When estrogen levels in this area dipped, the animals’ metabolic rate and energy also plummeted. The study found that the animals developed an impaired tolerance to glucose and gained weight even when their caloric intake remained the same. Furthermore, the excess weight went straight to their middle sections, creating an increase in visceral fat.

The team now plans to perform a similar experiment to deactivate ER-alpha in the arcuate nucleus region of the hypothalamus. This area contains two populations of neurons: one puts the brake on food intake and the other stimulates food intake.

The study was discussed on August 20 at the “234th National Meeting of the American Chemical Society.”

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