Circulating and cerebrospinal fluid ghrelin and leptin: potential role in altered body weight in Huntington's disease.
OBJECTIVE
In addition to neurological impairment, weight loss is a prominent characteristic of Huntington's disease (HD). Neuropathologically, the disease affects the caudate nucleus and the cerebral cortex, and also the hypothalamus. The recently discovered orexigenic hormone of gastric origin, ghrelin and the adipocyte hormone leptin, are two peripherally produced hormones exerting opposite effects on specific populations of hypothalamic neurons that play a key role in regulating energy intake and energy output. The aim of this study was to investigate the possible involvement of cerebrospinal fluid (CSF) and circulating ghrelin and leptin in the regulation of energy balance in patients with HD.


METHODS
Twenty healthy normal-weight subjects undergoing orthopedic surgery, and fifteen patients with genetically verified HD, were enrolled in this study. The unified Huntington's disease rating scale (UHDRS) was used to assess clinical course of the disease. Blood samples for hormonal measurements were obtained by venipuncture and in-parallel CSF samples for leptin/ghrelin determination were obtained by lumbar puncture.


RESULTS
Patients with HD had increased concentrations of ghrelin in plasma compared with healthy subjects (4523.7+/-563.9 vs 2781.1+/-306.2 pg/ml, P<0.01). On the other hand, patients with HD had decreased concentrations of leptin in plasma compared with healthy subjects (4.8+/-1.6 vs 10.9+/-2.4 ng/ml, P<0.01). The concentrations of CSF ghrelin and CSF leptin were equivalent to values in healthy subjects. No correlation was found between disease duration--and other clinical features of HD--and plasma or CSF leptin/ghrelin levels. In patients with HD, baseline levels of GH, IGF-I, insulin and glucose did not differ from those in healthy subjects.


CONCLUSIONS
High circulating ghrelin and low leptin levels in patients with HD suggest a state of negative energy balance. Early nutritional support of patients with HD is advocated since patients with HD and higher body mass index at presentation have slower progression of the disease.
Neuroendocrine Unit, Institute of Endocrinology, University Clinical Centre, Belgrade, Serbia. popver@Eunet.Yu
Vera
V
Popovic
Marina
M
Svetel
Marina
M
Djurovic
Smiljka
S
Petrovic
Mirjana
M
Doknic
Sandra
S
Pekic
Dragana
D
Miljic
Natasa
N
Milic
Jovana
J
Glodic
Carlos
C
Dieguez
Felipe F
FF
Casanueva
Vladimir
V
Kostic
D000328:Adult; D015992:Body Mass Index; D001835:Body Weight; D004734:Energy Metabolism; D005260:Female; D054439:Ghrelin; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D020738:Leptin / Q000097:blood / Q000134:cerebrospinal fluid*; D008297:Male; D008875:Middle Aged; D036361:Peptide Hormones / Q000097:blood / Q000134:cerebrospinal fluid*
D054439:Ghrelin; D020738:Leptin; D036361:Peptide Hormones