Role of orexin receptors in obesity: From cellular to behavioral evidence

C. E. Perez-Leighton, T. A. Butterick-Peterson, Charles J Billington, Catherine M Kotz

Research output: Contribution to journalReview articlepeer-review

22 Scopus citations


The orexin peptides and their two receptors are involved in multiple physiological processes, including energy homeostasis, arousal, stress and reward. Higher signaling of the orexin peptides at the orexin receptors (OXR) protects against obesity, but it is less clear how their activation in different brain regions contributes to this behavioral output. This review summarizes the evidence available for a role of central OXR in energy homeostasis and their contribution to obesity. A detailed analysis of anatomical, cellular and behavioral evidence shows that modulation of energy homeostasis by the OXR is largely dependent upon anatomical and cellular context. It also shows that obesity resistance provided by activation of the OXR is distributed across multiple brain sites with site-specific actions. We suggest that understanding the role of the OXR in the development of obesity requires considering both specific mechanisms within brain regions and interactions of orexinergic input between multiple sites.

Original languageEnglish (US)
Pages (from-to)167-174
Number of pages8
JournalInternational Journal of Obesity
Issue number2
StatePublished - Feb 2013

Bibliographical note

Funding Information:
We thank Dr Joshua Nixon, Dr Jennifer Teske and Dr Vijaya Mavanji for valuable discussions and suggestions to this article. This study was supported by funding from the National Institute of Health, NIDDK, DK078985.


  • diet-induced obesity
  • energy metabolism
  • hypothalamus
  • orexin
  • orexin receptors
  • spontaneous physical activity


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