The sex hormone estrogen has an important, if underappreciated, role in weight gain as women get older, say researchers in the journal Cell Metabolism. The researchers, from the University of Texas Southwestern Medical Center, traced estrogen's effects on metabolism to different parts of the brain.
"When women approach menopause, they gain weight in fat and their energy expenditure goes down," says researcher Deborah Clegg. "Estrogen levels decline and women grow increasingly susceptible to obesity and metabolic syndrome."
Estrogen acts on receptors found throughout the body, in fat, on ovaries and in muscle. But when it comes to the hormone's influence on metabolism, Clegg suspected receptors in the brain.
Other scientists had tracked the effects of estrogen on energy balance specifically to estrogen receptor-á (ERá). When Clegg's team "knocked out" (deleted) those receptors from the brains of mice, "we got very, very fat mice," she explained. "The animals consumed more calories and burned less."
Clegg showed that female mice lacking ERá in one part of the brain (the hypothalamic steroidogenic factor-1 or SF1 neurons) gained weight without eating any more. Loss of ERá from another brain area (the hypothalamic pro-opiomelanocortin or POMC neurons) had the opposite effect: animals ate more without gaining weight. Loss of ERá receptors in those same neurons also led to various problems in ovulation and fecundity.
Importantly, the findings may lead to the development of highly personalized hormone replacement therapies that specifically target estrogen receptors in the brain. Such therapies would offer a useful alternative to shotgun-style hormone replacement therapies that hit receptors throughout the body.
The researchers say they would like to continue to isolate other estrogen-related effects and symptoms, for instance, on hot flashes and cognition. "The more we know about estrogen's sites of action, the more likely it is we could develop designer hormone replacement therapies targeting tissue X, Y or Z," Clegg concluded.
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Source: Cell Press