February 5, 2009

A new obesity drug target is possible

U.S. medical researchers say they have discovered a possible new obesity drug target that doesn't involve altering brain function.

The researchers, led by University of North Carolina School of Medicine Professor Yi Zhang, said they discovered the gene Jhdm2a, when mutated, causes obesity by dampening the body's ability to burn energy while leaving appetite unaffected.

The finding, said Zhang, might lead to new pharmacologic approaches to treating obesity in humans.

The 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.

Zhang's says he believes the study involves the first mouse model to exhibit obese traits that don't result 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, he said. Therefore, we are really looking for a pure effect on metabolism.

The study that included Dr. Keisuke Tateishi, Yuki Okada and Eric Kallin appears online in the journal Nature.