Much research is devoted to uncovering why some people chronically overeat and how medicine might be able to help them. Severe childhood obesity may be caused by partial loss of a growth factor receptor, reports a study in the November issue of Nature Neuroscience.
Stephen O'Rahilly and colleagues, found in a severely obese and mildly retarded child that one of the two copies of the gene for the receptor TrkB was mutated and thereby rendered inactive. TrkB is present on the surface of nerve cells, where it binds the nervous system growth factor BDNF and transmits its signal to the cell interior. The BDNF/TrkB system is well known for its role in supporting the survival of nerve cells, and it was quite a surprise when a few years ago an American group of researchers showed that lack of BDNF or TrkB could cause severe obesity in mice.
The current paper's authors now report the first human in whom obesity may be caused by insufficient BDNF/TrkB signaling; their patient does not carry any mutations in other genes linked to obesity. The authors screened another 288 people with severe childhood-onset obesity for defects in the TrkB gene, and found five different mutations in five patients. These results do not yet prove that TrkB mutations are a significant cause of morbid obesity, but they do suggest that TrkB signaling is involved in body weight regulation, and that it could be a target for drug development.
Stephen O'Rahilly (Cambridge Institute for Medical Research and Addenbrooke's Hospital, University of Cambridge, UK)
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(C) Nature Neuroscience press release.
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