More brown fat to fight obesity?

More brown fat to fight obesity?

Two teams of researchers have discovered clues to the way mammals make and use white and brown fat cells that could lead to treatments for obesity and weight loss; for instance it could be that boosting brown fat cell production at the expense of white cells could increase the calorie burning as opposed to the calorie storing side of the body's energy balancing system.

The research teams have written up their work in two papers in the latest issue of Nature, published online on 21st August.

The bodies of mammals use body fat or adipose tissue to control energy balance by storing and burning calories. When mammals eat more calories than they need, their bodies make triglycerides and store them in white fat cells; this is the fat we all know about and remember with pangs of guilt (well, some of us) every time we bite into that slice of chocolate cake. But there is another type of fat that is not often talked about, perhaps because adult humans have far less of it compared to white fat, and that is brown fat or brown adipose tissue that burns energy and can counteract obesity.

White fat cells are basically sacs of stored triglycerides, waiting for a lean period to come along before they allow themselves to be opened up and burned for energy. Brown fat cells are quite different, they have a lot more mitochondria, the calorie burning "batteries" inside each cell that give cells energy to do their stuff. Mitochondria are full of iron-rich proteins which give brown fat cells their characteristic tinge.

But in adult humans white fat cells by far outnumber brown fat cells, as in several kilos of the former against mere grams of the latter, which are mostly concentrated in the front part of the neck and the upper chest. Newborn babies have pads of brown fat between their shoulder blades, like little energy heat sources (hot water bottles under the skin) to keep them warm, so many scientists believe. However, their role in adults is not clear.

Brown fat is so efficient at burning calories that around 50 grams of it could burn 20 per cent of a person's daily calorie intake, said Ronald Kahn of the Joslin Diabetes Center at Harvard Medical School in Boston, Massachusetts, and co-author of the study that examined how overexpression of a bone forming protein, BMP7, stopped mice gaining weight as quickly as controls fed the same diet. Kahn said with more time, the difference in weight between the two groups of mice would have been more marked (they stopped the experiment after a few days).

Brown fat is "a very efficient tissue at wasting energy", said Bruce Spiegelman of the Dana-Farber Cancer Institute and Harvard Medical School, "It's basically a fire that's just burning", he added. Spiegelman is co-author of the study where he and his team traced the origin of brown fat cells in mice, then found that by turning on a trigger protein called PRDM16 they could encourage myoblast cells that normally produce muscle cells to produce brown, but not white, fat cells instead. Contrary to what many scientists believed, they showed that brown and white fat cells didn't share similar origins.

Kahn and colleagues are currently testing BMP7 for healing bones after surgery. Because it is a bone forming protein it has to be used very carefully, he said. For example, in a weight loss application they would have to make sure using BMP7 produced brown fat cells without bone cells, or, as Kahn put it:

"You could have rock hard abs but not in the way you'd expected."

Spiegelman said the finding confirmed that PRDM16 was the "master regulator" of brown fat development and he and his team will now push for further research to see if drugs that increase the protein in mice could make white fat turn into brown fat, which would be a potential treatment for obesity. Another approach could be to transplant brown fat cells into a person who is overweight and help their body burn more calories.

"I think we now have very convincing evidence that PRDM16 can turn cells into brown fat cells, with the possibility of combating obesity," said Spiegelman.

While it is hoped these findings will open up opportunities for treating obesity, there is still a lot of work to be done to replicate these results in humans, where brown fat appears to behave quite differently.

Dominique Langin, a clinical biochemist based at the National Institute of Health and Medical Research (INSERM) in Toulouse, France, said that in large mammals like human beings, the brown fat is there at birth and then goes away, and then forms again in other places, and the role it plays in overall metabolism and energy balance is still unclear. This does not happen in mice, where the brown fat does not go through these shifts, and where it plays a clear role in keeping body temperature steady.

"PRDM16 controls a brown fat/skeletal muscle switch."

Patrick Seale, Bryan Bjork, Wenli Yang, Shingo Kajimura, Sherry Chin, Shihuan Kuang, Anthony Scimè, Srikripa Devarakonda, Heather M. Conroe, Hediye Erdjument-Bromage, Paul Tempst, Michael A. Rudnicki, David R. Beier & Bruce M. Spiegelman.

Nature, Volume, 454 Number 7207, pages 961-967, Published 21 August 2008.


Click here for Abstract.

"New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure."

Yu-Hua Tseng, Efi Kokkotou, Tim J. Schulz, Tian Lian Huang, Jonathon N. Winnay, Cullen M. Taniguchi, Thien T. Tran, Ryo Suzuki, Daniel O. Espinoza, Yuji Yamamoto, Molly J. Ahrens, Andrew T. Dudley, Andrew W. Norris, Rohit N. Kulkarni & C. Ronald Kahn.

Nature, Volume, 454 Number 7207, pages 1000-1004, Published 21 August 2008. DOI:10.1038/nature07221

Click here for Abstract.

Sources: Nature News, journal abstracts, Dana-Faber Cancer Institute.

Dr Paul Lee - Treating Diabetes and Obesity Through Brown Fat (Video Medical And Professional 2020).

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