Protein that stimulates brown fat could boost weight loss strategies

By Darren Quick May 14, 2012  For most of us fighting the battle of the bulge, fat is an enemy that must be reigned in to a healthier – and less noticeable – level. But there are actually two types of fat – or adipose tissue – found in mammals: white and brown. While white fat stores calories and is the culprit behind love handles, brown fat's primary function is to generate heat to keep the body warm through the burning of fats in a process known as thermogenesis. Therefore, the ability to activate brown fat in the body could provide a means to fight obesity and keep the weight off. Now scientists have discovered a protein that could allow them to do just that.  We recently covered the discovery at the US San Francisco Diabetes Center that a protein called PRDM16 appears to regulate the development of brown fat and could be used to promote the conversion of white fat cells to brown fat. Now scientists at the University of Cambridge Metabolic Research Laboratories at the Institute of Metabolic Science have discovered that another protein, called BMP8B, also plays a role in the regulation of brown fat and is also a potential therapeutic target in the fight against obesity.  Unlike PRDM16, which accumulates in white fat cells until a high enough concentration is reached to flip a gene-controlled switch that triggers a conversion to brown fat, BMP8B plays a role in the regulation of brown fat by acting on a specific metabolic system that operates in the brain and the tissues of the body.  "Other proteins made by the body can enhance heat production in brown fat, such as thyroid hormone but often these proteins have important effects in other organs too," said Dr Andrew Whittle. "Therefore they are not good targets for developing new weight loss treatments. However, BMP8B seems to be very specific for regulating the heat producing activity of brown fat, making it a more ideal mechanism for new therapies."  In experiments carried out by the researchers, mice lacking the BMP8B protein found it more difficult to maintain their normal body temperature and also become more obese than normal mice – especially when fed a high fat diet.  The researchers found that treating brown fat cells with BMP8B caused them to respond more strongly to activation by the nervous system. Additionally, when BMP8B was administered to specific parts of the brains of the mice, the amount of nervous activation of brown fat tissue increased. As a result, the fat cells treated with BMP8B burned more fat and the mice whose brains were administered with BMP8B lost weight.  "A major feature of current weight-loss strategies is that people lose a lot of weight early on, but then reach a plateau despite continuing to follow the same diet regime," said Professor Toni Vidal-Puig, lead author of the study. "This is because the human body is incredibly good at sensing a reduction in food consumption and slows the metabolic rate to compensate. A strategy to increase brown fat activity could potentially be used in conjunction with current weight loss strategies to help prevent the typical decrease in a person's metabolic rate."  Professor Vidal-Puig added that while the treatment made the mice lose weight by burning more fat in their brown adipose tissue, it didn't cause the mice to simply eat more to fuel the increase in metabolism.  "There are obvious differences between mice and humans, and from a therapeutic perspective this work is preliminary," Professor Vidal-Puig said. "Validation will be necessary to see if manipulating BMP8B would be safe and effective in humans."