Leptin secretion rate increases with higher CAG repeat number in Huntington's disease patients

P>Background Huntington's disease (HD) is a hereditary neurodegenerative disorder caused by an increased number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown. Objective To perform a detailed analysis of adipose tissue function in HD patients as abnormal fat tissue function could contribute to the weight loss. Design, setting and participants In a clinical research laboratory, 24-h plasma concentrations of leptin, adiponectin and resistin were studied in nine early-stage, medication-free HD patients and nine age-, gender- and body mass index (BMI)-matched controls. Measurements Leptin was measured every 20 min whereas adiponectin and resistin were measured hourly. Autodeconvolution and cosinor regression were applied to quantify secretion characteristics of leptin and diurnal variations in leptin, adiponectin and resistin levels. Results Plasma levels and diurnal rhythmicity of leptin, adiponectin and resistin were not significantly different between HD patients and controls. However, although leptin production increased with higher BMI and fat mass in controls, no such relation was present in HD patients. Moreover, when corrected for fat mass, mean plasma leptin concentration as well as basal, pulsatile and total secretion rates increased with the size of the CAG repeat mutation (r = +0 center dot 72 to r = +0 center dot 80; all P < 0 center dot 05). Both higher pulsatile leptin secretion and higher mean adiponectin levels were associated with a greater degree of motor and functional impairment in HD patients. Conclusions CAG-repeat size-dependent interference of the HD mutation with adipose tissue function may contribute to weight loss in HD patients.