Gender differences between hypocretin/orexin knockout and wild type mice: age, body weight, body composition, metabolic markers, leptin and insulin resistance
Version of Record online: 21 AUG 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 131, Issue 5, pages 615–624, December 2014
How to Cite
J. Neurochem. (2014) 131, 615–624.
- Issue online: 19 NOV 2014
- Version of Record online: 21 AUG 2014
- Accepted manuscript online: 28 JUL 2014 04:20AM EST
- Manuscript Accepted: 24 JUL 2014
- Manuscript Revised: 23 JUL 2014
- Manuscript Received: 18 MAY 2014
- National Institutes of Health. Grant Numbers: NS14610, MH64109
- Medical Research Service of the Department of Veterans Affairs
- body weight;
Female hypocretin knockout (Hcrt KO) mice have increased body weight despite decreased food intake compared to wild type (WT) mice. In order to understand the nature of the increased body weight, we carried out a detailed study of Hcrt KO and WT, male, and female mice. Female KO mice showed consistently higher body weight than WT mice, from 4 to 20 months (20–60%). Fat, muscle, and free fluid levels were all significantly higher in adult (7–9 months) as well as old (18–20 months) female KO mice compared to age-matched WT mice. Old male KO mice showed significantly higher fat content (150%) compared to age-matched WT mice, but no significant change in body weight. Respiratory quotient (−19%) and metabolic rates (−14%) were significantly lower in KO mice compared to WT mice, regardless of gender or age. Female KO mice had significantly higher serum leptin levels (191%) than WT mice at 18–20 months, but no difference between male mice were observed. Conversely, insulin resistance was significantly higher in both male (73%) and female (93%) KO mice compared to age- and sex-matched WT mice. We conclude that absence of the Hcrt peptide has gender-specific effects. In contrast, Hcrt-ataxin mice and human narcoleptics, with loss of the whole Hcrt cell, show weight gain in both sexes.
Female hypocretin knockout (Hcrt KO) mice show consistently higher body weight than female wild type (WT) mice, from 4 to 20 months. We report that this increase arises from the higher fat, muscle, and free fluid content of KO mice compared to WT mice. Male Hcrt KO mice did not show any significant changes in body weight throughout this time period. We conclude that absence of the Hcrt peptide has gender-specific effects. In contrast, Hcrt-ataxin mice and human narcoleptics, with loss of the whole Hcrt cell, show weight gain in both sexes.