Plasma Total Ghrelin and Leptin Levels in Human Narcolepsy and Matched Healthy Controls: Basal Concentrations and Response to Sodium Oxybate
1Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands; 2Department of Chemistry, Leiden University Medical Center, Leiden, The Netherlands; 3Department of Endocrinology, Leiden University Medical Center, Leiden, The Netherlands; 4Department of Neurology, Donders Institute for Neuroscience, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands; 5Center for Sleep Medicine, “Kempenhaeghe,” Heeze, The Netherlands
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.
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).
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.
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.
Donjacour CEHM; Pardi D; Aziz NA; Frölich M; Roelfsema F; Overeem S; Pijl H; Lammers GJ. Plasma total ghrelin and leptin levels in human narcolepsy and matched healthy controls: basal concentrations and response to sodium oxybate. J Clin Sleep Med 2013;9(8):797-803.
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