Experimental and Clinical Research Center, A Joint Cooperation between the Charité University Medicine Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
PLoS One. 2012;7(8):e43675. doi: 10.1371/journal.pone.0043675. Epub 2012 Aug 28.
Metabolic flexibility is defined as ability to adjust fuel oxidation to fuel availability. Multiple sclerosis (MS) results in reduced muscle strength and exercise intolerance. We tested the hypothesis that altered metabolic flexibility contributes to exercise intolerance in MS patients.
We studied 16 patients (all on glatiramer) and 16 matched healthy controls. Energy expenditure (EE), and carbohydrate (COX) and lipid oxidation (LOX) rates were determined by calorimetry, before and after an oral glucose load. We made measurements either at rest (canopy device) or during 40 min low-grade (0.5 W/kg) exercise (metabolic chamber). We also obtained plasma, and adipose tissue and skeletal muscle dialysate samples by microdialysis to study tissue-level metabolism under resting conditions.
At rest, fasting and postprandial plasma glucose, insulin, and free fatty acid levels did not differ between patients and controls. Fasting and postprandial COX was higher and LOX lower in patients. In adipose, fasting and postprandial dialysate glucose, lactate, and glycerol levels were higher in patients vs. controls. In muscle, fasting and postprandial dialysate metabolite levels did not differ significantly between the groups. During exercise, EE did not differ between the groups. However, COX increased sharply over 20 min in patients, without reaching a steady state, followed by an immediate decrease within the next 20 min and fell even below basal levels after exercise in patients, compared to controls.
Glucose tolerance is not impaired in MS patients. At rest, there is no indication for metabolic inflexibility or mitochondrial dysfunction in skeletal muscle. The increased adipose tissue lipolytic activity might result from glatiramer treatment. Autonomic dysfunction might cause dysregulation of postprandial thermogenesis at rest and lipid mobilization during exercise.
代谢灵活性定义为调整燃料氧化以适应燃料可用性的能力。多发性硬化症（MS）会导致肌肉力量下降和运动不耐受。我们检验了这样一个假设，即代谢灵活性的改变导致 MS 患者运动不耐受。
我们研究了 16 名患者（均接受格拉替雷治疗）和 16 名匹配的健康对照者。通过热量测定法在口服葡萄糖负荷前后测定能量消耗（EE）以及碳水化合物（COX）和脂质氧化（LOX）率。我们在休息时（天幕装置）或在 40 分钟低强度（0.5 W/kg）运动（代谢室）时进行测量。我们还通过微透析获得了血浆、脂肪组织和骨骼肌透析液样本，以研究休息状态下的组织代谢。
在休息时，患者和对照组的空腹和餐后血浆葡萄糖、胰岛素和游离脂肪酸水平没有差异。患者的空腹和餐后 COX 更高，LOX 更低。在脂肪组织中，患者的空腹和餐后透析液葡萄糖、乳酸和甘油水平高于对照组。在肌肉中，两组的空腹和餐后透析液代谢物水平没有显著差异。在运动期间，两组的 EE 没有差异。然而，在患者中，COX 在 20 分钟内急剧增加，但未达到稳定状态，随后在下一个 20 分钟内立即下降，甚至在运动后低于基础水平，而对照组则没有。
MS 患者的葡萄糖耐量没有受损。在休息时，骨骼肌没有代谢灵活性或线粒体功能障碍的迹象。增加的脂肪组织脂肪分解活性可能是由于格拉替雷治疗所致。自主神经功能障碍可能导致餐后产热在休息时和运动时的脂质动员失调。
