New research on the effects of the female sex hormone estrogen in the brain lend credence to what many women have suspected about the hormonal changes that accompany aging—namely that menopause causes weight gain in most women. Scientists have long sought to understand how changes in hormones during menopause could account for the increase in appetite and accompanying weight gain that often occurs among aging women.
From Dr. Cederquist; In my practice, I find a high correlation with menopause and the onset of insulin resistance in women who have been previously insulin sensitive. Treating insulin resistance with specific dietary, exercise and medication recommendations has been effective for my patients and will remain the treatment of choice until further research proves safe and effective ways to modulate the estrogen receptors that promote weight gain.
As described at the 234th meeting of the American Chemical Society, researchers used a series of animal experiments to show how estrogen receptors located in the hypothalamus serve as a master switch to control food intake, energy expenditure, and body fat distribution. The research showed that when these receptors are disabled, the animals immediately begin to eat more food, burn less energy, and pack on pounds.
The research seems to support the link between estrogen and regulation of obesity, especially the dangerous accumulation of abdominal fat, which is linked to heart disease, diabetes, and cancer. Scientists are hoping that these findings may also lead to the development of more targeted hormone replacement therapies, capable of stimulating estrogen receptors in one part of the brain or body while dampening it in the next. Specific estrogen receptors were evaluated, including the estrogen receptor alpha, or ER-alpha, which plays a role in regulating food intake and energy expenditure.
Continuing studies are being performed at the University of Cincinnati. To determine the effect of dwindling estrogen levels in the brain, researchers are focusing on two ER-alpha rich regions located in the hypothalamus, specifically in the ventromedial nucleus (VMN), which is a key center for energy regulation.
Using gene-silencing RNA interference, the researchers deactivated the ER-alpha receptors in the VMN, while the estrogen receptors in other regions of the brain maintained their normal capacity. They found that when estrogen levels in the VMN dipped, the animals’ metabolic rate and energy levels also plummeted. The findings show the animals quickly developed an impaired tolerance to glucose and a sizable weight gain, even when their calorie intake remained the same. Additionally, the excess weight went straight to the abdomen, creating an increase in visceral fat.
The findings suggested that the ER-alpha receptors in this region play an essential role in controlling energy balance, body fat distribution, and normal body weight. Further studies are planned to perform similar experiments to deactivate the ER-alpha receptors in the arcuate nucleus region of the hypothalamus. This region contains two populations of neurons: one stops food intake and the other stimulates food intake. It is anticipated that a loss of estrogen in this region may create an increase in the animals’ appetites as well as their weight.
Studies in this area are needed given the incidence and impact of gender differences in obesity and its complications. The accumulation of abdominal fat puts both men and women at a heightened risk of cardiovascular disease, diabetes, and insulin resistance. When menopause occurs and body fat shifts to the abdomen, women find themselves no longer protected from these negative consequences as they were in younger years when body fat was primarily carried in the hips and thighs.
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