Plasma total ghrelin and leptin levels in human narcolepsy and matched healthy controls: basal concentrations and response to sodium oxybate.
OBJECTIVE
Narcolepsy is caused by a selective loss of hypocretin neurons and is associated with obesity. Ghrelin and leptin interact with hypocretin neurons to influence energy homeostasis. Here, we evaluated whether human hypocretin deficiency, or the narcolepsy therapeutic agent sodium oxybate, alter the levels of these hormones.


METHODS
Eight male, medication free, hypocretin deficient, narcolepsy with cataplexy patients, and 8 healthy controls matched for age, sex, body mass index (BMI), waisttohip ratio, and body fat percentage were assessed. Blood samples of total ghrelin and leptin were collected over 24 hours at 60 and 20-min intervals, respectively, during 2 study occasions: baseline, and during the last night of 5 consecutive nights of sodium oxybate administration (2 × 3.0 g/night).


RESULTS
At baseline, mean 24-h total ghrelin (936 ± 142 vs. 949 ± 175 pg/mL, p = 0.873) and leptin (115 ± 5.0 vs. 79.0 ± 32 mg/L, p = 0.18) levels were not different between hypocretin deficient narcolepsy patients and controls. Furthermore, sodium oxybate did not significantly affect the plasma concentration of either one of these hormones.


CONCLUSIONS
The increased BMI of narcolepsy patients is unlikely to be mediated by hypocretin deficiency-mediated alterations in total ghrelin or leptin levels. Thus, the effects of these hormones on hypocretin neurons may be mainly unidirectional. Although sodium oxybate may influence body weight, the underlying mechanism is unlikely to involve changes in total ghrelin or leptin secretion.
Department of Neurology, Leiden University Medical Center, The Netherlands.
Claire E H M
CE
Donjacour
Daniel
D
Pardi
N Ahmad
NA
Aziz
Marijke
M
Frölich
Ferdinand
F
Roelfsema
Sebastiaan
S
Overeem
Hanno
H
Pijl
Gert Jan
GJ
Lammers
D000759:Adjuvants, Anesthesia / Q000097:blood / Q000627:therapeutic use; D000328:Adult; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D054439:Ghrelin / Q000097:blood*; D006801:Humans; D020738:Leptin / Q000097:blood*; D008297:Male; D009290:Narcolepsy / Q000097:blood* / Q000188:drug therapy*; D009765:Obesity / Q000097:blood; D012978:Sodium Oxybate / Q000097:blood* / Q000627:therapeutic use*
D000759:Adjuvants, Anesthesia; D054439:Ghrelin; D020738:Leptin; D012978:Sodium Oxybate
Ghrelin; hypocretin; leptin; narcolepsy; orexin; sodium oxybate