Washington: Researchers have discovered a new genetic cause of severe obesity which, although relatively rare, demonstrates for the first time that genes can reduce basal metabolic rate.
In collaboration with Dr Ines Barroso's team at the Wellcome Trust Sanger Institute, the researchers sequenced the DNA from over 2,000 severely obese patients and identified multiple mutations in the KSR2 gene.
KSR2 belongs to a group of proteins called scaffolding proteins which play a critical role in ensuring that signals from hormones such as insulin are correctly processed by cells in the body to regulate how cells grow, divide and use energy.
To investigate how KSR2 mutations might lead to obesity, Professor Sadaf Farooqi from the University of Cambridge's Wellcome Trust-MRC Institute of Metabolic Science and his team performed a series of experiments which showed that many of the mutations disrupt these cellular signals and, importantly, reduce the ability of cells to use glucose and fatty acids.
Patients who had the mutations in KSR2 had an increased drive to eat in childhood, but also a reduced metabolic rate, indicating that they have a reduced ability to use up all the energy that they consume.
The findings in this study provide the first evidence that defects in a particular gene, KSR2, can affect a person's metabolic rate and how their bodies processed calories.
"Up until now, the genes we have identified that control body weight have largely affected appetite. However, KSR2 is different in that it also plays a role in regulating how energy is used in the body. In the future, modulation of KSR2 may represent a useful therapeutic strategy for obesity and type 2 diabetes," Farooqi said.
The research was published online today, 24 October, in the journal Cell.
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