title: Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions.
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.
authors.affiliation: Institute of Basic Medical Sciences, Department of Pharmacology, University of Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Hara
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakurai
mesh_terms: D000818:Animals; D001069:Appetite Regulation / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000235:genetics; D004777:Environment; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D007026:Hypothalamic Area, Lateral / Q000473:pathology / Q000503:physiopathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009290:Narcolepsy / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D009479:Neuropeptides / Q000235:genetics*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D000068797:Orexins; D010641:Phenotype; D013045:Species Specificity
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins