Sex difference in body weight gain and leptin signaling in hypocretin/orexin deficient mouse models

Nobuhiro Fujiki, Yasushi Yoshida, Shengwen Zhang, Takeshi Sakurai, Masashi Yanagisawa, Seiji Nishino

Research output: Contribution to journalArticlepeer-review

42 Scopus citations


Recent studies in human and animal models of narcolepsy have suggested that obesity in narcolepsy may be due to deficiency of hypocretin signaling, and is also under the influence of environmental factors and the genetic background. In the current study, using two hypocretin/orexin deficient narcoleptic mouse models (i.e. preproorexin knockout (KO) and orexin/ataxin-3 transgenic (TG) mice) with cross-sectional assessments, we have further analyzed factors affecting obesity. We found that both KO and TG narcoleptic mice with mixed genetic backgrounds (N4-5, 93.75-96.88% genetic composition of C57BL/6) tended to be heavier than wild type (WT) mice of 100-200 days old. The body weight of heterozygous mice was intermediate between those of KO and WT mice. Obesity was more prominent in females in both KO and TG narcoleptic mice and was associated with higher serum leptin levels, suggesting a partial leptin resistance. Obesity is less prominent in the congenic TG narcoleptic mice, but is still evident in females. Our results confirmed that hypocretin/orexin ligand deficiency is one of the critical factors for the obese tendency in narcolepsy. However, multiple factors are also likely to affect this phenotype, and a sex difference specific alteration of leptin-hypocretin signaling may be involved.

Original languageEnglish (US)
Pages (from-to)2326-2331
Number of pages6
Issue number9
StatePublished - Sep 2006


  • Hypocretin
  • Leptin
  • Narcolepsy
  • Obesity
  • Orexin
  • Sex difference

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience


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