Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions

Junko Hara, Masashi Yanagisawa, Takeshi Sakurai

Research output: Contribution to journalArticlepeer-review

167 Scopus citations

Abstract

Orexins are a pair of neuropeptides expressed by a population of neurons located in the lateral hypothalamic area (LHA). Prepro-orexin- or orexin receptor type 2-deficient animals exhibit a phenotype remarkably similar to the human sleep disorder, narcolepsy, which is characterized by sleep/wakefulness fragmentation. Human narcolepsy is known to be associated with metabolic abnormalities, including an increased frequency of obesity and non-insulin-dependent diabetes mellitus. Complex disruption of energy homeostasis in orexin neuron-deficient transgenic mice (orexin/ataxin-3 mice) is also manifested as late-onset obesity despite eating less. Here, we report that the development of obesity in orexin neuron-ablated narcoleptic mice is critically dependent on their genetic background and environmental factors, and the phenotype is different from that of prepro-orexin knockout mice even under the same genetic background and environmental factors, suggesting that factors that co-localize in orexin neurons might have important roles in the regulation of energy homeostasis. Our observation also suggests that the obesity observed in orexin neuron-deficient narcolepsy is dependent on the genetic background and environmental factors.

Original languageEnglish (US)
Pages (from-to)239-242
Number of pages4
JournalNeuroscience letters
Volume380
Issue number3
DOIs
StatePublished - Jun 3 2005

Keywords

  • Body weight
  • Energy homeostasis
  • Genetic background
  • Obesity
  • Orexin

ASJC Scopus subject areas

  • General Neuroscience

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