Oestrogen 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 oestrogen 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, Gynaecology & Reproductive Sciences at Yale School of Medicine.
Horvath and his team studied the regulation of obesity in mice with mutations in leptin or oestrogen signalling. They analysed the effect of oestrogen on the ability of nerve cells to make new connections in the hypothalamus. They also measured the associated feeding behaviour and energy expenditure of the animals. According to their report, oestrogen is a strong regulator of energy metabolism through the brain. They show that while the pathway of oestrogen-induced intracellular signalling merges with that of leptin, oestrogen's effect on feeding and obesity is independent from leptin or the leptin receptor. "Impaired oestrogen signalling in the brain may be the cause of metabolic changes during menopause," said Horvath. "Brain-selective mimics of oestrogen could be a viable approach to tackle obesity in the case of leptin resistance." In previous studies, Horvath and his team found that that oestrogen induces synaptic plasticity in the hypothalamus, so they looked to see whether those alterations by oestrogen were in line with the proposed shift in the activity of the hypothalamus. In future studies, Horvath and his team will analyse brain-specific mimics of oestrogen on metabolism, obesity in particular. "Brain-specific oestrogen analogs would allow us to take advantage of oestradiol's weight reducing effects without altering peripheral tissues such as the breast and ovaries," said Horvath.(Source: Nature Medicine : Yale School of Medicine : January 2007.)