StemCell Therapy

Nature has its way of keeping things in balance. When it comes to body weight, the key regulator is leptin, a hormone secreted by fat cells. When fat storage increases, leptin informs the brain to lower appetiteand vice versa. Thats how the body balances its fat stores and food intake, keeping them within a fine range.

In some people, however, the system miscalculates. For the past 25 years, since leptin was first discovered by Rockefellers Jeffrey M. Friedman, scientists have wanted to understand exactly how changes in the hormones function may lead to obesity, an ever-worsening public health problem that now affects more than 650 million adults worldwide. Some have suggested that the disease is caused by problems in leptins faithful reporting of fat levels to the brain; others have argued that it is in fact due to the brains failure to respond to the hormone.

It turns out this internal calibrator can go kaput in different ways in different people.

In a study published in Nature Medicine earlier this year, Friedman, the Marilyn M. Simpson Professor, and his collaborators suggest that at least 10 percent of obese people may be genetically incapable of producing sufficient leptin at all. No matter how much fat is stored in the body, their leptin levels remain low.

These people have less leptin from an early age, making them a little bit hungrier than everyone else, says Olof Dallner, a research associate and the lead author of the study.

A typical leptin-deficient mouse weighs 1.94 times more than the average lab mouse.

The researchers traced the problem to a type of RNA that seems to regulate how much leptin is produced. When the team engineered mice without this specific RNA, and fed them a high-fat diet, the mice kept accumulating fat to the point of becoming obese, but their leptin levels nevertheless remained low. Another group of unaltered mice munching on the same unhealthy diet became a little chubby, toobut this group produced normal amounts of leptin, which appears to have kept them from becoming outright obese.

Theres compelling evidence that these findings might pertain to humans, too. When the team looked at the genetic profiles of more than 46,000 people, they found that alterations in the human version of the same RNA are linked with lower leptin levels. Some people, this work suggests, may have a subtype of obesity thats potentially treatable with leptin therapy. That was indeed the case with the low-leptin mice: When the animals received injections of leptin, they lost weight.

All of this is good news for people with leptin-curbing mutations. But most obese people gain weight not because of too little leptin but because their brain has stopped responding to it. For this group, there may be other avenues for therapyfor example, targeting the brain networks that control not just how much we eat, but also how much energy we burn.

In a recent study published in Cell, Friedmans team identified a group of neurons in the brain stem that do just that. In mice, turning the neurons off triggers the burning of fat to produce body heat, and also decreases hunger. It suggests that these multitalented cells could be powerful levers for managing body weightespecially if they could be targeted with drugs.

See the original post here:
When zombies take over the brain - The Rockefeller University Newswire

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