Fat metabolism during exercise in patients with mitochondrial disease.
OBJECTIVE
To determine whether patients with defects of the respiratory chain have metabolic adaptations that promote a preferential use of fats or carbohydrates, similar to what is observed in metabolic myopathies affecting glycolysis or fat oxidation.


METHODS
Causation and case-control study. Fat metabolism was determined by means of indirect calorimetry and stable isotope technique in patients and healthy subjects. Patients carried various types and loads (mean [SE], 72% [5%]) of mitochondrial DNA (mtDNA) mutations in skeletal muscle. All subjects exercised at the same absolute workload (mean [SE], 65 [10] W), corresponding to 72% (in patients) and 30% (in healthy subjects) of maximum oxygen consumption.


METHODS
Neuromuscular research unit.


METHODS
Ten patients with mtDNA mutations and 10 sex-matched healthy subjects.


METHODS
Fat turnover, plasma concentrations of palmitate and total free fatty acids, glucose mobilization, and total carbohydrate oxidation.


RESULTS
Fat turnover and plasma concentrations of palmitate and total free fatty acids were similar in patients and healthy subjects at rest and during exercise. In line with the higher relative workload of the patients, glucose mobilization and total carbohydrate oxidation were higher in the patients compared with the healthy subjects.


CONCLUSIONS
During moderate-intensity exercise, the balance between fat and carbohydrate use in patients with mtDNA mutations matches that seen in healthy subjects, indicating that manipulating dietary fat and carbohydrate content is not a feasible therapeutic option to improve exercise intolerance in these disorders.
Jeppesen
Tina Dysgaard
TD
Department of Neurology and Copenhagen Muscle Research Center, University of Copenhagen, Rigshospitalet, Denmark.
Orngreen
Mette Cathrine
MC
van Hall
Gerrit
G
Haller
Ronald G
RG
Vissing
John
J
D000328:Adult; D050260:Carbohydrate Metabolism; D016022:Case-Control Studies; D004579:Electron Transport; D004837:Epinephrine / Q000097:blood; D015444:Exercise / Q000502:physiology*; D005227:Fatty Acids / Q000097:blood*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000097:blood / Q000503:physiopathology* / Q000534:rehabilitation*; D018482:Muscle, Skeletal; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption; D019308:Palmitic Acid / Q000097:blood
D005227:Fatty Acids; D006728:Hormones; D007328:Insulin; D019308:Palmitic Acid; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine