Orexin B

Orexin B

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Orexin B is a naturally occurring linear peptide composed of 28 amino acids. It is generated by proteolytic cleavage of the prepro-orexin (prepro-hypocretin) precursor in neurons of the lateral hypothalamus and is one of two endogenous orexin (hypocretin) neuropeptides, alongside Orexin A.

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Orexin B preferentially activates the Orexin Receptor 2 (OX2R), although it can also bind OX1R with lower affinity. Because of its receptor selectivity, Orexin B is used in experimental models to investigate sleep-wake regulation, arousal, feeding behaviour, energy homeostasis, and reward-related neural signalling in both in vitro and in vivo research.

The role of this neuropeptide in regulating the sleep-wake cycle is well established through studies using genetically modified rodent models with altered orexin signalling. The consistency between many preclinical findings and clinical observations supports the translational value of these models, particularly for advancing sleep disorder research.

Orexin B’s role in appetite regulation and long-term energy homeostasis is more complex. Although rodent studies provide valuable mechanistic insights, translating these findings to human obesity and metabolic disorders requires careful consideration of broader physiological and environmental factors.

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