Feeding the heat on brown fat.

Nutrition plays a dominant role in human adaptation. Biological traits conferring these adaptations are of considerable significance. Within an obesogenic environment, there is considerable variation among individuals in their susceptibility to weight gain. Some individuals rapidly gain weight, whereas others remain lean without any conscious effort, suggesting that obesity pathogenesis may not be centered on just the primal feeding behavior. The ability of certain individuals to subconsciously resist obesity reveals adaptive calorie-burning mechanisms that may promote fitness. Here, we review a fat-burning mechanism that is turned on by the brain hormone orexin during high-caloric food consumption. Remarkably, the same hormone also induces feeding, and its levels correlate with lean body mass in both rodents and humans. Intriguingly, loss of orexin prevents thermogenic energy expenditure while inducing obesity in the face of hypophagia. Thus, orexin is a unique neuropeptide that promotes both feeding and energy expenditure, conferring resistance to weight gain. Mechanisms that safely augment orexin signaling may have potential in antiobesity therapeutics.