Scientists working at The Rockefeller University in New York City, and the Joslin Diabetes Center in Boston, have identified a gene that counteracts obesity. The gene, Foxa-2, which is expressed in immature fat cells (pre-adipocytes) and in mature adipocytes of genetically and diet-induced obese mice, prevents pre-adipocyte differentiation and increases metabolism in mature adipocytes. The findings are reported in The Journal of Clinical Investigation.

“We know a lot about the various molecular pathways that stimulate or promote fat production, and the focus has been on trying to block these pathways to fight obesity” says Markus Stoffel, of Rockefeller University, the lead investigator in the study. “This pathway is one of only a few that we know of that naturally work to counteract obesity” (ScienceDaily, 16 July 2003).

Overexpressing Foxa-2 in cultured pre-adipocytes inhibits differentiation by activating transcription of Pref-1. This, in turn, prevents the adipocyte maturing. In mature adipocytes, as well as activating Pref-1, Foxa-2 also seemed to activate other genes that are involved in fat and glucose metabolism and so might feature in diet-induced insulin-resistance and benefit type 2 diabetic patients, too.

“It is now apparent that when we overfeed a mouse and it becomes obese, Foxa-2 is induced, which then activates a set of genes that work against obesity,” says Stoffel. “Obviously that's not sufficient to prevent obesity, but it is sufficient to slow it down. Without this force, the mice accumulate more fat.” (Yahoo News, 21 July 2003). The next challenge is to identify what induces Foxa-2 expression in humans.