Leptin secretion rate increases with higher CAG repeat number in Huntington's disease patients
Leptin secretion rate increases with higher CAG repeat number in Huntington's disease patients
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DOI：
10.1111/j.1365-2265.2009.03661.x
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发表时间：
2010-08-01
影响因子：
3.2
通讯作者：
Roos, Raymund A. C.
中科院分区：
文献类型：
--
作者：
Aziz, N. Ahmad;Pijl, Hanno;Roos, Raymund A. C.
亨廷顿病（Huntington 'sdisease，HD）是一种遗传性神经退行性疾病，由亨廷顿基因CAG重复序列数目增加引起。HD的一个标志是非预期的体重减轻，其原因尚不清楚。测量每20分钟测量一次瘦素，而每小时测量一次脂联素和瘦素。Autodeconvolution和余弦回归被施加到量化的瘦素分泌特性和昼夜变化的瘦素，脂联素和lipoprotein level.Resultsplasma水平和昼夜节律的瘦素，脂联素和lipoprotein HD患者和对照组之间没有显着差异。然而，尽管在对照组中瘦素的产生随着BMI和脂肪量的增加而增加，但在HD患者中不存在这种关系。此外，当校正脂肪质量时，平均血浆瘦素浓度以及基础、脉动和总分泌速率随着CAG重复突变的大小而增加（r = +0中心点72至r = +0中心点80;所有P < 0中心点05）。更高的脉动瘦素分泌和更高的平均脂联素水平与更大程度的运动和功能障碍HD patients. ConclusionsCAG重复序列大小依赖的干扰HD突变与脂肪组织功能可能有助于体重减轻HD患者。
P>BackgroundHuntington'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.ObjectiveTo 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 participantsIn 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.MeasurementsLeptin 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.ResultsPlasma 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.ConclusionsCAG-repeat size-dependent interference of the HD mutation with adipose tissue function may contribute to weight loss in HD patients.