In an article in the April 15 issue of the journal Genes & Development, Jeffrey M. Friedman, Investigator of the Howard Hughes Medical Institute, and his team at The Rockefeller University, provide clues as to how a hormone that regulates body weight works. By scanning thousands of genes from obese mice, they discovered a group of genes that are specifically regulated by the hormone leptin. Obesity is a major health concern in the US. In this country alone, one in five adults suffer from obesity. Studies on how leptin works to control body weight could provide therapeutic targets in the battle of the bulge.
Leptin is produced by fat tissue and secreted into the bloodstream, working its way to the brain and other tissues where it carries out its job by sending a message to stop eating and to burn more fat. Mice that lack leptin are obese, weighing nearly three times more than their normal counterparts. When these obese mice are given hormone treatments, they lose weight in part because they eat less but there is another component to their weight loss that is not known.
To discover why leptin causes additional weight loss, Friedman and colleagues used oligonucleotide microarrays, popularly known as 'gene chips'. These tiny chips, containing thousands of gene fragments, are bathed in a solution containing messenger RNA from two different sources. In this instance, samples were taken from normal mice and mice with little or no natural leptin, after they were treated with the hormone. After mice lacking leptin were given the hormone, their fat cells changed the profile of gene expression in a distinct way, indicating that at least part of the effects of leptin are due to a regulation of gene expression. Many genes appeared that were known to be regulated by a protein named SREBP-1, including SREBP-1 itself. SREBP-1 is known to play a role in controlling fatty acid synthesis. In addition to SREBP-1, other genes involved in fatty acid synthesis were identified
Contact: Joseph Bonner
Cold Spring Harbor Laboratory