Immune to weight loss

Leptin always seemed a bit too good to be true. Why would our chronically undernourished ancestors have evolved a hormone for weight loss? Now, Ke Chen, Allan Zhao (University of Pittsburgh, PA), and colleagues explain why leptin doesn't work as the weight loss wonder drug that initially seemed a possibility.

Leptin was discovered as a hormone produced by fat cells. When reinstated in leptin-deficient mice and humans it drastically reduced their obesity. But individuals who were obese for other reasons had paradoxically high leptin levels, and adding more leptin did not induce significant weight loss.

The Pittsburgh group looked to leptin-binding proteins for an answer. The first that they found was C-reactive protein (CRP), which is famous as a marker for immune reactions but whose exact function remains mysterious. CRP bound to leptin, and inhibited leptin signaling...