Credit: Biophoto Associates/Photo Researchers, Inc.

Deficiency in orexin neuropeptide hormones has been linked to narcolepsy, a sleep disorder. People with narcolepsy are more likely to be obese, but how this occurs is unclear, as they do not eat more or exercise less than normal individuals. A recent study (Cell Metab. 14, 478–489) suggests that orexin's effects on metabolism might be mediated by regulating brown adipose tissue (BAT).

Dyan Sellayah et al. found that wild-type mice undergo a compensatory increase in metabolic rate in response to a high-fat diet, but orexin-null narcoleptic mice failed to adapt their metabolism accordingly. The authors showed that this is because orexin is required for the differentiation of brown adipocyte precursors. An absence of orexin impaired the thermogenic capacity of brown fat, which can normally function as a mechanism to counteract weight gain. The BAT developmental defect in orexin-null neonates could be rescued by injecting orexin to their orexin-null mothers.

Although orexin is unlikely to be a therapeutic option for treating obesity, due to its complex effects on the brain, further investigation of the pathways controlled by orexin in BAT may allow the discovery of new therapeutic targets based on BAT expansion, activation or both.