The cause for obesity lies in the functioning of a certain gene, reports a team of American researchers. They have found that this gene, when mutated, hinders the body's ability to burn energy while leaving the appetite unaffected.
Researchers at the University of North Carolina at Chapel Hill School of Medicine say that this study could potentially lead to new pharmacologic approaches to treating obesity in humans that do not target the brain.
The findings also add new knowledge to the growing 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, study's senior author Yi Zhang, Ph.D. showed that Jhdm2a was able to demethylate, or 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.
The new study focused on a line of so-called "knockout" mice that lacked the Jhdm2a gene.
Zhang found impairment in two molecular signaling pathways important for normal function in brown fat tissue and muscle cells.
Both pathways exert a major influence on metabolism, the body's conversion of food to energy. Without the enzyme, the mice had reduced metabolisms, becoming visibly obese.
According to Zhang', this is the first mouse model to exhibit obese traits that do not resulting from an alteration in appetite, which is largely a brain function.
"Given that this gene is not expressed in the brain, any drug that targets this gene would not have an effect on brain function. Therefore, we are really looking for a pure effect on metabolism," Nature quoted him, as saying.
With that in mind, Zhang anticipates that the study 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.
The study is published online February 4, 2009 in the journal Nature.