In search of fat profits

With at least 400 million people worldwide judged to be obese,1 the hard pressed personal trainer needs an assistant. But not necessarily someone else in shorts and running shoes, badgering overweight people to do five minutes more on the exercise bike. The new help—out of sight, and in a laboratory somewhere—could be a “chemical metabolic engineer.”

Pharmacological attempts to tackle obesity are nothing new. Thyroid hormones have long been known to cause weight loss; unfortunately, that is not all they do. But the molecular biology of metabolic control has moved rapidly during the past decade or so. This is perhaps why Ronald Evans, speaking to the 2007 experimental biology meeting in Washington, DC, at the end of April, felt sufficiently confident about the future to invoke that bold concept of chemical metabolic engineering.

Professor Evans runs the gene expression laboratory at the Salk Institute in La Jolla, California. The genes he studies include a family that code for peroxisome proliferator activated receptors (PPARs). Different members of the PPAR family have different functions. One called PPARδ, his current preoccupation, seems to act as a master regulator of the body's metabolism. Its activity determines whether the body's cells store fat or burn it.

Professor Evans has shown the role of PPARδ through genetic manipulation.2 He has created mice in which the gene, instead of being switched on when required to regulate the body's fat stores, remains in the “on” position all the time. These modified mice weigh 20-35% less than their normal counterparts eating the same diet. They are also resistant to high fat diets that would otherwise make them …