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Researchers at Yale School of Medicine say that estrogen, the main female sex hormone, is involved in the regulation of 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.
"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.
The research team investigated the regulation of obesity in mice with mutations in leptin or estrogen signaling. They checked the effect of estrogen on the ability of neurons to make new connections in the hypothalamus and also measured the associated feeding behavior and energy expenditure of the animals.
They discovered that estrogen is a strong regulator of energy metabolism through the brain. But while the pathway of estrogen-induced intracellular signaling is the same 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."
Previously, the same team discovered 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.
The researchers are going to investigate 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.