February 6, 2009
Scientists at the University of North Carolina at Chapel Hill School of Medicine have discovered a gene that when mutated causes obesity by dampening the body's ability to burn energy while leaving appetite unaffected.
The new research could potentially lead to new drugs for treating obesity that do not target the brain, according to study senior author Yi Zhang, Ph.D., Howard Hughes Medical Institute investigator and professor of biochemistry and biophysics in the UNC School of Medicine.
The findings also add new knowledge to the burgeoning field of epigenetics, in which heritable changes in gene expression or physical appearance are caused by mechanisms besides changes in the underlying DNA.
The gene in question encodes for a specific epigenetic factor, an enzyme called Jhdm2a. In 2006, Zhang showed that Jhdm2a was able to remove a methyl group from one of four histone proteins bound to all genes. Because they are so intimately associated with DNA, even slight chemical alterations of histones can have profound effects on nearby genes.
Zhang anticipates that the study, published online February 4, 2009 in the journal Nature, could be of great interest to pharmaceutical companies eager to develop new anti-obesity drugs aimed at a novel, new molecular target expressed in non-brain tissues.
Zhang said his group will continue to look for more detailed mechanisms involved in how the enzyme regulates the relevant genes and changes in the metabolic rate.
