title: Plasma obestatin and autonomic function are altered in orexin-deficient narcolepsy, but ghrelin is unchanged.
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.
authors.affiliation: University of Liverpool Diabetes and Endocrinology Research Group, Clinical Sciences Centre, University Hospital Aintree, Liverpool, L9 7AL, UK. bobby.huda@bartshealth.nhs.uk
authors.forename: M S B
authors.initials: MS
authors.lastname: Huda
authors.forename: H
authors.initials: H
authors.lastname: Mani
authors.forename: B H
authors.initials: BH
authors.lastname: Durham
authors.forename: T M
authors.initials: TM
authors.lastname: Dovey
authors.forename: J C G
authors.initials: JC
authors.lastname: Halford
authors.forename: B S
authors.initials: BS
authors.lastname: Aditya
authors.forename: J H
authors.initials: JH
authors.lastname: Pinkney
authors.forename: J P
authors.initials: JP
authors.lastname: Wilding
authors.forename: I K
authors.initials: IK
authors.lastname: Hart
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology*; D005215:Fasting / Q000097:blood; D005260:Female; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000097:blood / Q000172:deficiency*; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000097:blood* / Q000503:physiopathology; D009479:Neuropeptides / Q000097:blood / Q000172:deficiency*; D000068797:Orexins; D019518:Postprandial Period
chemical_list: D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins