April 16, 2004
Weight Loss Strategy: Drugs To Turn White Fat Into Brown Fat

Study of sheep fat cell development may lead to a drug that can burn the fat off of overweight humans.

The way newborn lambs regulate their temperature in the first few weeks of life using a special deposit of brown fat could give clues for tackling obesity in humans, according to Imperial College London scientists.

Unlike normal white fat that stores surplus energy, brown fat generates heat in response to cold or excess caloric intake. While some mammals such as rodents maintain this 'good' fat throughout life, humans are similar to lambs: brown fat is present in the newborn to act as an internal central heating system maintaining body temperature and preventing hypothermia, but rapidly disappears as brown fat is irreversibly replaced by normal white fat.

Now, researchers based at Imperial's Wye campus in Kent are determining the molecular switch in lambs that transforms brown fat into normal white fat, and investigations are underway to determine whether this conversion could be reversed and used as a new fat busting technique.

Professor Michael Lomax, head of Imperial's Animal Science Research section at Wye and leader of the project says:

"Obesity is fast becoming one of the biggest problems for the Western world. In the UK statistics suggest 20 per cent of us are overweight and in the USA the situation is even worse with more than 60 per cent of the population either overweight or clinically obese.

"While researchers continue to investigate how to increase the body's natural appetite suppressants most of us at some point will have resorted to some kind of diet to move those couple of extra stubborn pounds. But by reactivating natural brown fat we could lose weight without even trying.

...

In most cells, mitochondria use the energy they liberate to make ATP, the fuel that drives chemical reactions in living organisms. But in brown fat cells, Uncoupling Protein 1 (UCP-1) interferes with this process, forcing the cells to release energy as heat. However, researchers are unsure how the molecular switch is flicked during development, turning UCP-1 expression off after birth in some mammals and not others.

During development so called master fat determination genes or PPARs govern whether an immature cell commits to becoming a fat cell, explains Dr Fouzia Sadiq of Imperial's Animal Science Research section.

"A further signal, PGC- 1 alpha is then needed to convert immature fat cells into brown fat that expresses UCP-1 rather than normal white fat," she says.

"But what we don't know is the underlying mechanism that regulates the loss of UCP-1 activity after birth. If we can establish this then we will be in a much better position to understand how to switch back on the signals that make immature fat cells develop into brown fat."

To establish whether PPARs and PGC-1 alpha play a role in switching UCP-1 off the researchers looked at expression levels during late pregnancy and over the first month after birth. The results indicate that levels of UCP-1 closely mirror levels of PPARs and PGC-1 alpha, suggesting that they are the key switches that control conversion of immature fat cells into brown rather than white fat.

"Having established the key role of PPARs and PGC-1 alpha we're now focusing on what drugs and natural compounds could reverse the process," says Dr Sadiq.

"Already the drug isoprenaline has been shown to increases levels of PGC-1 alpha and PPARs with a subsequent increase UCP-1 after birth. Now we're looking at whether synthetic and natural activators of the genes that express PPARs and PGC-1 alpha have the same effect."

Obesity is a consequence of the fact that we humans no longer live in the environments that we evolved to be adapted to. The rising prevalence of obesity is a sign of just how maladapted we are to modern life. Another less noticed sign of maladaptation is the physical reaction many experience when in an argument in a business meeting. When the adrenaline rushes through your body and your body becomes ready for "fight or flight" you are experiencing a maladaptive response. You aren't going to fight and you aren't going go running down the hallway to escape. The stress of each "fight or flight" response is causing damage to accumulate that ages the body and it would be good to be able to avoidi that stress by suppressing the physiological reaction to anger and frustration.

To avoid getting overweight in the first place the development of effective appetite suppression drugs seem to be what is called for. However, for those already overweight the ability to turn up one's fat cells to burn off the fat as heat would be very valuable. Of course, that will generate more heat. So once methods of converting white fat cells into heat-generating brown fat cells are developed one can even imagine someone saying "I'm going to take off these pounds as soon as the weather gets cold enough".

Drugs that would turn up heat generation from fat cells would also have value for those who have to work outside in cold weather.

Think about what the future will look like once weight control becomes possible by use of safe pharmaceuticals. Obesity will become rare. Given that substantial advances are being made in our understanding of both appetite and fat cell operation and also given that the rate of advance in biotechnology as a whole is accelerating it seems most likely that 20 years from now obesity will be a rare condition and mostly will be found either in people who want to be fat for some reason (e.g. for a movie role or for an extreme cold weather sport) or who have some unusual desire to be fat.

Before obesity becomes a rare condition I expect we will first witness the near total disappearance of both corrective glasses and contact lenses. While LASIK and other technologies for reshaping lenses are making some in-roads in fixing eyesight problems the real promising advances are coming from the ability to replace aged hard lenses with soft and flexible lenses. See my previous posts on this here and here.

Share |      Randall Parker, 2004 April 16 01:12 PM  Bodies Perfected


Comments
nectarflowed said at October 2, 2004 12:56 AM:

Don't generating heat and other metabolic processes also generate aging-causing oxygen free-radicals? ..although scandinavia does have one of the longest average life expectencies.

Dave said at April 11, 2009 8:55 AM:

recent studies in 2009 have found that humans actually retain brown fat for life. more lean people have more of it.

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