title: Is metabolic flexibility altered in multiple sclerosis patients?
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Experimental and Clinical Research Center, A Joint Cooperation between the Charité University Medicine Berlin and Max Delbrueck Center for Molecular Medicine, Berlin, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Mähler
authors.forename: Jochen
authors.initials: J
authors.lastname: Steiniger
authors.forename: Markus
authors.initials: M
authors.lastname: Bock
authors.forename: Alexander U
authors.initials: AU
authors.lastname: Brandt
authors.forename: Verena
authors.initials: V
authors.lastname: Haas
authors.forename: Michael
authors.initials: M
authors.lastname: Boschmann
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
mesh_terms: D000328:Adult; D050260:Carbohydrate Metabolism / Q000187:drug effects; D016022:Case-Control Studies; D059305:Diet, High-Fat / Q000009:adverse effects; D004040:Dietary Carbohydrates / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005215:Fasting; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000150:complications / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D004040:Dietary Carbohydrates