Estrogen regulates the brain's energy metabolism in the same way as the hormone leptin, leading the way to a viable approach to tackling obesity in people resistant to leptin, researchers at Yale School of Medicine report in the December 31 online issue of Nature Medicine.
"We found that estrogen suppresses appetite using the same pathways in the brain as the adipose hormone leptin," said lead author Tamas L. Horvath, chair and professor of Comparative Medicine and professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.
Horvath and his team studied the regulation of obesity in mice with mutations in leptin or estrogen signaling. They analyzed the effect of estrogen on the ability of nerve cells to make new connections in the hypothalamus. They also measured the associated feeding behavior and energy expenditure of the animals.
According to their report, estrogen is a strong regulator of energy metabolism through the brain. They show that while the pathway of estrogen-induced intracellular signaling merges with that of leptin, estrogen's effect on feeding and obesity is independent from leptin or the leptin receptor.
"Impaired estrogen signaling in the brain may be the cause of metabolic changes during menopause," said Horvath. "Brain-selective mimics of estrogen could be a viable approach to tackle obesity in the case of leptin resistance."
In previous studies, Horvath and his team found that that estrogen induces synaptic plasticity in the hypothalamus, so they looked to see whether those alterations by estrogen were in line with the proposed shift in the activity of the hypothalamus.
In future studies, Horvath and his team will analyze brain-specific mimics of estrogen on metabolism, obesity in particular. "Brain-specific estrogen analogs would allow us to take advantage of estradiol's weight reducing effects without altering peripheral tissues such as the breast and ovaries," said Horvath.
Other authors on the study included Qian Gao, Gabor Mezei, Yongzhan Nie, Yan Rao, Cheol Soo Choi, Ingo Bechmann, Csaba Leranth, Dominique Torran-Allerand, Catherine A Priest, James L Roberts, Xiao-Bing Gao, Charles Mobbs, Gerald I. Shulman and Sabrina Diano.
The study was supported by grants from the National Institutes of Health.
Citation: Nature Medicine Online (December 31, 2006)
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