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Low cerebrospinal fluid hypocretin (orexin) and altered energy homeostasis in human narcolepsy
Author(s) -
Nishino Seiji,
Ripley Beth,
Overeem Sebastiaan,
Nevsimalova Sona,
Lammers Gert Jan,
Vankova Jitka,
Okun Michele,
Rogers William,
Brooks Stephen,
Mignot Emmanuel
Publication year - 2001
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.1130
Subject(s) - narcolepsy , orexin , medicine , leptin , energy homeostasis , endocrinology , homeostasis , cerebrospinal fluid , cataplexy , neuropeptide , orexin a , human leukocyte antigen , neurology , antigen , immunology , receptor , obesity , psychiatry
Hypocretins (orexins) are hypothalamic neuropeptides involved in sleep and energy homeostasis. Hypocretin mutations produce narcolepsy in animal models. In humans, narcolepsy is rarely due to hypocretin mutations, but this system is deficient in the cerebrospinal fluid (CSF) and brain of a small number of patients. A recent study also indicates increased body mass index (BMI) in narcolepsy. The sensitivity of low CSF hypocretin was examined in 38 successive narcolepsy–cataplexy cases [36 human leukocyte antigen (HLA)‐DQB1*0602‐positive] and 34 matched controls (15 controls and 19 neurological patients). BMI and CSF leptin levels were also measured. Hypocretin‐1 was measurable (169 to 376pg/ml) in all controls. Levels were unaffected by freezing/thawing or prolonged storage and did not display any concentration gradient. Hypocretin‐1 was dramatically decreased (<100pg/ml) in 32 of 38 patients (all HLA‐positive). Four patients had normal levels (2 HLA‐negative). Two HLA‐positive patients had high levels (609 and 637pg/ml). CSF leptin and adjusted BMI were significantly higher in patients versus controls. We conclude that the hypocretin ligand is deficient in most cases of human narcolepsy, providing possible diagnostic applications. Increased BMI and leptin indicate altered energy homeostasis. Sleep and energy metabolism are likely to be functionally connected through the hypocretin system.