Hypothalamic Orexin Stimulates Feeding-Associated Glucose Utilization in Skeletal Muscle via Sympathetic Nervous System

Tetsuya Shiuchi, Mohammad Shahidul Haque, Shiki Okamoto, Tsuyoshi Inoue, Haruaki Kageyama, Suni Lee, Chitoku Toda, Atsushi Suzuki, Eric S. Bachman, Young Bum Kim, Takashi Sakurai, Masashi Yanagisawa, Seiji Shioda, Keiji Imoto, Yasuhiko Minokoshi

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149 Scopus citations

Abstract

Hypothalamic neurons containing orexin (hypocretin) are activated during motivated behaviors and active waking. We show that injection of orexin-A into the ventromedial hypothalamus (VMH) of mice or rats increased glucose uptake and promoted insulin-induced glucose uptake and glycogen synthesis in skeletal muscle, but not in white adipose tissue, by activating the sympathetic nervous system. These effects of orexin were blunted in mice lacking β-adrenergic receptors but were restored by forced expression of the β2-adrenergic receptor in both myocytes and nonmyocyte cells of skeletal muscle. Orexin neurons are activated by conditioned sweet tasting and directly excite VMH neurons, thereby increasing muscle glucose metabolism and its insulin sensitivity. Orexin and its receptor in VMH thus play a key role in the regulation of muscle glucose metabolism associated with highly motivated behavior by activating muscle sympathetic nerves and β2-adrenergic signaling.

Original languageEnglish (US)
Pages (from-to)466-480
Number of pages15
JournalCell Metabolism
Volume10
Issue number6
DOIs
StatePublished - Dec 2 2009

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Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Shiuchi, T., Haque, M. S., Okamoto, S., Inoue, T., Kageyama, H., Lee, S., Toda, C., Suzuki, A., Bachman, E. S., Kim, Y. B., Sakurai, T., Yanagisawa, M., Shioda, S., Imoto, K., & Minokoshi, Y. (2009). Hypothalamic Orexin Stimulates Feeding-Associated Glucose Utilization in Skeletal Muscle via Sympathetic Nervous System. Cell Metabolism, 10(6), 466-480. https://doi.org/10.1016/j.cmet.2009.09.013