Abstract
Carbohydrate availability affects fat metabolism during exercise; however, the effects of complete muscle glycogen unavailability on maximal fat oxidation (MFO) rate remain unknown. Our purpose was to examine the MFO rate in patients with McArdle disease, comprising an inherited condition caused by complete blockade of muscle glycogen metabolism, compared to healthy controls. Nine patients (three women, aged 36 ± 12 years) and 12 healthy controls (four women, aged 40 ± 13 years) were studied. Several molecular markers of lipid transport/metabolism were also determined in skeletal muscle (gastrocnemius) and white adipose tissue of McArdle (Pygm p.50R*/p.50R*) and wild-type male mice. Peak oxygen uptake ( ˙VO2peakV̇O2peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$<math> <semantics> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> <annotation>${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$</annotation></semantics> </math> ), MFO rate, the exercise intensity eliciting MFO rate (FATmax) and the MFO rate-associated workload were determined by indirect calorimetry during an incremental cycle-ergometer test. Despite having a much lower ˙VO2peakV̇O2peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$<math> <semantics> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> <annotation>${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$</annotation></semantics> </math> (24.7 ± 4 vs. 42.5 ± 11.4 mL kg-1 min-1 , respectively; P < 0.0001), patients showed considerably higher values for the MFO rate (0.53 ± 0.12 vs. 0.33 ± 0.10 g min-1 , P = 0.001), and for the FATmax (94.4 ± 7.2 vs. 41.3 ± 9.1 % of ˙VO2peakV̇O2peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$<math> <semantics> <msub><mover><mi>V</mi> <mo>̇</mo></mover> <mrow><msub><mi>O</mi> <mn>2</mn></msub> <mi>peak</mi></mrow> </msub> <annotation>${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$</annotation></semantics> </math> , P < 0.0001) and MFO rate-associated workload (1.33 ± 0.35 vs. 0.81 ± 0.54 W kg-1 , P = 0.020) than controls. No between-group differences were found overall in molecular markers of lipid transport/metabolism in mice. In summary, patients with McArdle disease show an exceptionally high MFO rate, which they attained at near-maximal exercise capacity. Pending more mechanistic explanations, these findings support the influence of glycogen availability on MFO rate and suggest that these patients develop a unique fat oxidation capacity, possibly as an adaptation to compensate for the inherited blockade in glycogen metabolism, and point to MFO rate as a potential limiting factor of exercise tolerance in this disease. KEY POINTS: Physically active McArdle patients show an exceptional fat oxidation capacity. Maximal fat oxidation rate occurs near-maximal exercise capacity in these patients. McArdle patients' exercise tolerance might rely on maximal fat oxidation rate capacity. Hyperpnoea might cloud substrate oxidation measurements in some patients. An animal model revealed overall no higher molecular markers of lipid transport/metabolism.