Scientists at the University of North Carolina at Chapel Hill School of Medicine have discovered a gene that when absent causes obesity by dampening the body’s ability to burn energy while leaving appetite unaffected.
The study focused on a line of knockout mice that lacked the Jhdm2a gene. They found that two molecular signaling pathways that are important for normal function in brown fat tissue and muscle cells were impaired. Both pathways exert a major influence on metabolism. Without the enzyme, the mice had reduced metabolisms, becoming visibly obese.
In addition to being obese, the Jhdm2a knockout mouse also developed other characteristics related to human metabolic disorder, such as hyperlipidemia and insulin resistance.
This is the first mouse model to exhibit obese traits that do not result from an alteration in appetite, which is largely a brain function, according to the scientists. “Given that this gene is not expressed in the brain, any drug that targets this gene would not have an effect on brain function,” points out senior author, Yi Zhang, Ph.D., Howard Hughes Medical Institute investigator and professor of biochemistry and biophysics.
Next the researchers plan to look for how the enzyme regulates the relevant genes and changes in the metabolic rate. They will conduct experiments with conditional knockout mouse models, in which the gene of interest is functionally removed from specific tissues such as, in this case, brown fat or muscle tissue.
The research was published online February 4 in Nature.