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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 × 10(5) ± 0.2 × 10(5) vs. control 3.3 × 10(5) ± 0.6 × 10(5 )ms(2)/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 R (2) = 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.
Original languageEnglish
Pages (from-to)696-704
Number of pages0
JournalEndocrine
Volume43
Issue number3
DOIs
Publication statusPublished - Jun 2013

Keywords

  • Adult
  • Autonomic Nervous System
  • Fasting
  • Female
  • Ghrelin
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Middle Aged
  • Narcolepsy
  • Neuropeptides
  • Orexins
  • Postprandial Period

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