Role of orexin in the central regulation of glucose and energy homeostasis

Hiroshi Tsuneki, Tsutomu Wada, Toshiyasu Sasaoka*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

56 Scopus citations

Abstract

Hypothalamic orexin neurons are known to regulate sleep/wake stability, feeding behavior, emotions, autonomic nerve activity, and whole-body energy metabolism. In addition, emerging evidence indicates that orexin contributes to central regulation of glucose homeostasis. Intriguingly, central administration of orexin is reported to cause blood glucose-elevating effect or blood glucose-lowering effect in rodents, depending on the experimental conditions. Here we reviewed the recent reports regarding the mode and mechanism of actions of orexin on these two opposing effects, and discuss the functional signifcance for the maintenance of glucose homeostasis. The fact that orexin exhibits biphasic effects on autonomic nerve activity and lipolysis suggests that orexin dually regulates the glucose appearance. In fact, orexin neurons are activated not only depending on the demand for glucose but also according to a circadian rhythm in the suprachiasmatic nucleus. The excited orexin neurons appear to alter the sympathetic or parasympathetic outfow to the periphery, and modulate the glucose production and utilization. Furthermore, defciency of orexin action, particularly reduction of orexin 2 receptor-signaling, disrupts the mechanism for protection against insulin resistance associated with aging or induced by chronic high fat feeding in mice. Taken together, hypothalamic orexin system may manage multiple tasks to coordinate the interconnection among the arousal, feeding, circadian, and glucose homeostasis pathways.

Original languageEnglish
Pages (from-to)365-374
Number of pages10
JournalEndocrine Journal
Volume59
Issue number5
DOIs
StatePublished - 2012

Keywords

  • Glucose metabolism
  • Hypothalamus
  • Insulin
  • Leptin
  • Orexin/hypocretin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Fingerprint

Dive into the research topics of 'Role of orexin in the central regulation of glucose and energy homeostasis'. Together they form a unique fingerprint.

Cite this