Researchers at the University of Michigan have identified a gene that appears to control obesity in mice, and have shown that by switching the gene off, mice remained thin even though they were fed a high-fat diet that should have led to obesity.
The gene – called IKKE – produces a protein kinase that functions to control other proteins. These proteins in turn regulate mouse metabolism by acting to switch other genes on and off as required and so changing the mouse’s metabolic rate.
Alan Saltiel, of the University of Michigan Life Sciences Institute said: “If follow-up studies show that IKKE is tied to obesity in humans, the gene and the protein it makes will be prime targets for the development of drugs to treat obesity, diabetes and complications associated with these disorders”.
When a mouse is fed a high fat diet, IKKE protein kinase levels rise, the metabolic rate slows and the animal gains weight. Studies involving knockout mice, where the IKKE gene is switched off so that the IKKE protein kinase cannot be synthesised, showed no weight gain when fed the high fat diet, but showed instead an increase in metabolism so that the extra calories were used up rather than stored as fat. It would appear that IKKE protein kinase acts as a brake on the metabolism when there is exposure to extra calories.
Saltiel and his team are now searching for small molecules that could inhibit IKKE protein kinase to see if inhibition of the protein has the same effect as deactivating the gene.
By Georgina Lavender