Estrogen in the Brain Prevents Obesity, Glucose Intolerance in Menopause

Researchers at the University of Cincinnati (UC) have found that adding estrogen in the brain may improve metabolic health in obese females.

The study conducted by Christina Estrada, a doctoral candidate in the UC psychology graduate program in the laboratory of Matia Solomon, PhD, an associate professor in the UC Department of Psychiatry and Behavioral Neuroscience, used animal models with menopause (surgically-induced) to induce obesity. The findings will be presented this week at the annual meeting of the Society for the Study of Ingestive Behavior (SSIB), the leading society for research encompassing all aspects of eating and drinking behavior. 

"We know as women age and enter into menopause, they tend to gain body weight and body fat, particularly in the abdominal or ‘belly’ area. Excess abdominal fat greatly increases risk for cardio-metabolic diseases,” says Solomon. "While there are likely many factors that are associated with these risks in menopausal women, estrogen loss is associated with body weight and fat gain during menopause. In fact, estrogen treatment can offset this weight gain in many women. For decades, we have known that estrogen regulates energy balance in brain areas like the hypothalamus. Many people don’t think about the brain as a regulator of body weight; however, overall metabolic health is maintained by crosstalk between the brain and the body.” 

Because in the brain, the medial amygdala (MeA) regulates body weight and contains an abundance of estrogen receptors (molecules that respond to estrogen), the researchers focused their attention on the MeA as a target area to prevent metabolic risk factors, commonly associated with menopause. The researchers used an animal model of surgical menopause by removing the ovaries and delivered estrogen directly in the MeA. Compared to placebo, estrogen treatment in the MeA prevented weight and abdominal fat gain and improved glucose tolerance in models without ovaries, suggesting this region is as an important target for the estrogen-mediated effects on metabolic health in menopausal females. 

"Obesity is a national epidemic and women are becoming obese at younger ages. Given the beneficial effects of estrogen on metabolic health, we were interested in determining the consequences of obesity on estrogen-related endpoints … akin to younger, premenopausal women,” says Estrada. A separate group of female animal models with intact ovaries were placed on a high-fat diet. Relative to their lean counterparts, obese females had increased blood estrogen levels, irregular reproductive cycles and altered estrogen receptor expression in brain regions regulating metabolic function including the hypothalamus and MeA. 

These findings suggest obesity may dampen the metabolically beneficial effects of estrogen in the body and in the brain in females. 

"These findings are particularly important because we know very little about the impact of obesity on brain function in women,” Estrada says, adding that the research team believes understanding how the brain and body work together to regulate metabolic health offers a more holistic perspective of how to tackle obesity prevention in women. The researchers say more studies are needed to address this, and the team is focused on understanding how obesity impacts brain health in females and whether these changes are temporary or permanent.