Endocrine

, Volume 43, Issue 3, pp 696–704

Plasma obestatin and autonomic function are altered in orexin-deficient narcolepsy, but ghrelin is unchanged

  • M. S. B. Huda
  • H. Mani
  • B. H. Durham
  • T. M. Dovey
  • J. C. G. Halford
  • B. S. Aditya
  • J. H. Pinkney
  • J. P. Wilding
  • I. K. Hart
Original Article

DOI: 10.1007/s12020-012-9838-1

Cite this article as:
Huda, M.S.B., Mani, H., Durham, B.H. et al. Endocrine (2013) 43: 696. doi:10.1007/s12020-012-9838-1
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Abstract

Narcolepsy–cataplexy is characterised by orexin deficiency, sleep disturbance, obesity and dysautonomia. Ghrelin and obestatin affect both energy intake and sleep. Our aim was to investigate ghrelin, obestatin and metabolic/autonomic function in narcolepsy–cataplexy. Eight narcolepsy–cataplexy patients (seven CSF orexin-deficient) and eight matched controls were studied. The subjects had a fixed energy meal with serial blood samples and measurement of heart rate variability (HRV). Fasting plasma obestatin was more than threefold higher in narcolepsy subjects (narcolepsy 89.6 ± 16 pg/ml vs. control 24.9 ± 3 pg/ml, p < 0.001). There was no change in HRV total power, but post-prandial low-frequency (LF) power and high-frequency (HF) power were lower in the narcolepsy group [area under the curve (AUC): HF power narcolepsy 1.4 × 105 ± 0.2 × 105 vs. control 3.3 × 105 ± 0.6 × 10ms2/h, p < 0.001]. On multiple regression analyses, the only significant predictor of plasma obestatin was HF power, which was inversely correlated with obestatin (β = −0.65 R2 = 38 %, p = 0.009). Fasting and post-prandial plasma ghrelin were similar in both groups (narcolepsy 589.5 ± 88 pg/ml vs. control 686.9 ± 81 pg/ml, p = 0.5; post-prandial AUC—narcolepsy 161.3 ± 22 ng/ml/min vs. control 188.6 ± 62 ng/ml/min, p = 0.4). Only the narcolepsy group had significant suppression of plasma ghrelin after the meal (ANOVA, p = 0.004). In orexin-deficient narcolepsy, fasting plasma ghrelin is unaltered, and post-prandial suppression is preserved. Fasting plasma obestatin is increased and correlates with autonomic dysfunction. As obestatin affects NREM sleep, we suggest that increased plasma levels contribute to the disrupted sleep-state control in narcolepsy.

Keywords

Narcolepsy Ghrelin Obestatin Autonomic dysfunction 

Abbreviations

ANOVA

Analyses of variance

AUC

Area under the curve

BMI

Body mass index

EDTA

Ethylene diamine tetraacetic acid

RMR

Resting metabolic rate

RQ

Respiratory quotient

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • M. S. B. Huda
    • 1
  • H. Mani
    • 1
  • B. H. Durham
    • 2
  • T. M. Dovey
    • 3
  • J. C. G. Halford
    • 3
  • B. S. Aditya
    • 1
  • J. H. Pinkney
    • 1
  • J. P. Wilding
    • 1
  • I. K. Hart
    • 4
  1. 1.University of Liverpool Diabetes and Endocrinology Research Group, Clinical Sciences CentreUniversity Hospital AintreeLiverpoolUK
  2. 2.Department of Clinical ChemistryRoyal Liverpool University HospitalLiverpoolUK
  3. 3.School of PsychologyUniversity of LiverpoolLiverpoolUK
  4. 4.University Division of NeuroscienceWalton Centre for Neurology and NeurosurgeryLiverpoolUK

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