Roles for Orexin/Hypocretin in the Control of Energy Balance and Metabolism

  • Paulette B. Goforth
  • Martin G. MyersEmail author
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 33)


The neuropeptide hypocretin is also commonly referred to as orexin, since its orexigenic action was recognized early. Orexin/hypocretin (OX) neurons project widely throughout the brain and the physiologic and behavioral functions of OX are much more complex than initially conceived based upon the stimulation of feeding. OX most notably controls functions relevant to attention, alertness, and motivation. OX also plays multiple crucial roles in the control of food intake, metabolism, and overall energy balance in mammals. OX signaling not only promotes food-seeking behavior upon short-term fasting to increase food intake and defend body weight, but, conversely, OX signaling also supports energy expenditure to protect against obesity. Furthermore, OX modulates the autonomic nervous system to control glucose metabolism, including during the response to hypoglycemia. Consistently, a variety of nutritional cues (including the hormones leptin and ghrelin) and metabolites (e.g., glucose, amino acids) control OX neurons. In this chapter, we review the control of OX neurons by nutritional/metabolic cues, along with our current understanding of the mechanisms by which OX and OX neurons contribute to the control of energy balance and metabolism.


Energy expenditure Food intake Glucose homeostasis Orexin/hypocretin 


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Authors and Affiliations

  1. 1.Department of PharmacologyUniversity of MichiganAnn ArborUSA
  2. 2.Departments of Internal Medicine, and Molecular and Integrative PhysiologyUniversity of MichiganAnn ArborUSA

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