Finding an unlikely culprit in weight gain

The notion that blocking the reproductive hormone FSH could reduce abdominal fat and slow bone loss after menopause has received the attention of researchers.
The notion that blocking the reproductive hormone FSH could reduce abdominal fat and slow bone loss after menopause has received the attention of researchers.PHOTO: ISTOCKPHOTO

Mouse studies point the finger at FSH but researchers are sceptical

For middle-aged women struggling with their weight, a recent spate of scientific findings sounds too good to be true. And they may be, researchers caution.

Studies in mice indicate that a single hormone whose levels rise at menopause could be responsible for a characteristic redistribution of weight in middle age to the abdomen, turning many women from "pears" to "apples".

At the same time, the hormone may spur the loss of bone.

In mouse studies, blocking the hormone solves those problems, increasing the calories burned, reducing abdominal fat, slowing bone loss and even encouraging physical activity.

The notion that such a simple intervention could solve two big problems of menopause has received the attention of researchers and has prompted commentaries in prestigious journals like The New England Journal Of Medicine and Cell Metabolism.

"It's a super interesting idea," said Dr Daniel Bessesen, an obesity expert and professor of medicine at the University of Colorado School of Medicine. With obesity rising, "we definitely need some new ideas".

The work began when Dr Mone Zaidi, a professor of medicine at the Icahn School of Medicine at Mount Sinai in New York City, became curious about whether a reproductive hormone - FSH, or follicle-stimulating hormone - affects bone density.

It had long been assumed that the hormone's role was limited to reproduction. FSH stimulates the production of eggs in women and sperm in men.

Researchers knew that blood levels of FSH soar as women's ovaries start to fail before menopause.

At the same time, women rapidly lose bone - even when blood levels of oestrogen, which can preserve bone, remain steady.

Dr Zaidi reasoned that FSH could be a culprit in bone loss. So he and his colleagues created an antibody that blocked FSH in female mice whose ovaries had been removed.

Since the mice were making no oestrogen at all, they ought to have been losing bone. Indeed, the bone marrow in such mice usually fills with fat instead of developing bone cells. Much the same happens in women: That is why their bones become less dense.

But in Dr Zaidi's laboratory, the mice that received the antibody did not develop fat-filled bone marrow and, to his enormous surprise, they lost large amounts of fat.

"This is a weird, weird finding," he recalled telling his friend, Dr Clifford J. Rosen, a bone specialist at Maine Medical Centre Research Institute. Dr Zaidi persuaded Dr Rosen to help repeat the experiments independently, each in his own lab.

At first, Dr Rosen was dubious: "I said, 'I don't believe it, I think it's not going to work, and it will cost a lot of money.'" But he received a grant for the research, and the two labs got started.

They had their results 21/2 years later - and they replicated Dr Zaidi's original findings.

The researchers also came up with a theory that might explain increased metabolic rates in mice in which FSH is blocked.

There are two kinds of fat in the body: white fat primarily stores energy, and brown fat burns calories and throws off heat.

Brown fat is more common in children, but researchers have found that adults also carry small amounts. In the experimental mice, white fat was being converted to brown fat.

At the moment, Dr Rosen is withholding judgment about whether the results will apply to humans.

"I think the idea has some credibility," he said. "But does it mean anything? I don't know."

But these are not the only researchers to find a link between obesity and the strange interplay of hormones.

Dr Wendy Kohrt, a professor of medicine at the University of Colorado, has been studying the effects of menopause on women's body fat and the amount of calories women burn. Dr Kohrt has given healthy pre-menopausal women a drug that blocks production of oestrogen and FSH, putting them into a reversible state of menopause.

Within five months, she found, the women's fat moves to their abdomens, increasing by 11 per cent on average. And they burn 50 fewer calories per day. The effect is reversed when the participants stop taking the drug or when Dr Kohrt gives them oestrogen.

Something similar goes on in men, although it is not clear that FSH is the sole cause, said Dr Michael W. Schwartz, director of the Nutrition Obesity Research Centre at the University of Washington.

Men with advanced prostate cancer often take Lupron, a drug intended to stop the production of testosterone, which can fuel their tumours. Often, they gain weight, accumulating fat in their abdomens. Lupron also blocks production of FSH, and the mouse studies suggest that this should prevent weight gain. That might be because of the loss of testosterone.

Yet in experiments in which men were given both Lupron and testosterone - leaving FSH the only blocked hormone - they still did not lose weight. FSH clearly is not the only factor at work, then.

But the dream of an easy way to prevent abdominal weight gain is so appealing, you just want it to be true, said Dr Philipp E. Scherer, a professor of internal medicine at the University of Texas Southwestern Medical Centre.

He has seen too many mouse studies fail in humans to be persuaded that this one will succeed. "I will be on the sidelines waiting," he said.

Dr Zaidi is undeterred. He is already preparing to test an anti-FSH antibody in people. "Whether it works in humans, I have absolutely no idea," he said.


A version of this article appeared in the print edition of The Straits Times on August 18, 2017, with the headline 'Finding an unlikely culprit in weight gain'. Print Edition | Subscribe