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

Neurosci Lett. 2005 Jun 3;380(3):239-42. doi: 10.1016/j.neulet.2005.01.046. Epub 2005 Feb 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Appetite Regulation / genetics
  • Body Weight / genetics
  • Disease Models, Animal
  • Energy Metabolism / genetics
  • Environment
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Hypothalamic Area, Lateral / pathology
  • Hypothalamic Area, Lateral / physiopathology*
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Narcolepsy / genetics
  • Narcolepsy / metabolism*
  • Narcolepsy / physiopathology
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / physiopathology
  • Neurons / metabolism*
  • Neurons / pathology
  • Neuropeptides / genetics*
  • Obesity / genetics*
  • Obesity / metabolism
  • Obesity / physiopathology
  • Orexins
  • Phenotype
  • Species Specificity


  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Orexins