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Nemec 2017 MiP2017

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Three-month exercise modulates functional state of muscle mitochondria in patients with mild cognitive impairment.

Link: MiP2017

Nemec M, Maderova D, Krumpolec P, Sedliak M, Cvecka J, Tirpakova V, Slobodova L, Schoen M, Sumbalova Z, Ukropcova B, Ukropec J (2017)

Event: MiP2017

COST Action MITOEAGLE

Sedentary ageing accelerates the risk of neurodegenerative and metabolic diseases. Three-month supervised aerobic/strength exercise intervention to 12 seniors with/without mild cognitive impairment was performed to examine changes in the whole body metabolism and muscle mitochondrial functions in association with cognitive state.

Glucose metabolism was examined by oGTT, insulin sensitivity by euglycemic hyperinsulinemic clamp; Resting Energy Expenditure (REE), metabolic substrate preference (RQ) and flexibility (ΔRQ) by indirect calorimetry (Ergostik, Geratherm Respiratory). Cognitive functions were assessed with a battery of validated cognitive tests (MMSE, CogState, Memtrax). Daily ambulatory activity was monitored by accelerometers (Activinsights). Biopsy of m. vastus lateralis was performed in local anaesthesia using Bergström technique and functional state of muscle mitochondria was measured by O2k high-resolution respirometry (Oroboros) applying SUIT protocols RP1 and RP2 [1]. Oxygen consumption rate (pmol/(s.mg) tissue wet weight) was evaluated in saponin-permeabilized muscle fibers.

Exercise training led to an increase in baseline respiration rate (leak state with Pyruvate+Malate; p=0,001) and complex I+II linked substrate respiratory state (RP1: p=0,036 and RP2: p=0,022). Complex I activity decreased irrespective of the substrate nature (RP1: p=0,025 and RP2: p=0,001). Moreover, increase in mitochondrial respiration was associated with higher ambulatory activity and improvements in metabolic flexibility which was documented by changes in steady state RQ (clamp; p=0,001). Improvements in metabolic flexibility were paralleled by higher baseline respiration rate (R=0,519; p=0,023), and negatively correlated with the clamp-induced increase in energy expenditure (R=-0,510; p=0,026). Interestingly, the baseline respiration rate was positively associated with a short-term memory (Cogstate, R=0,420; p=0,023) and negatively with the time to complete the Trail Making Test (R=-0,388; p=0,038). In addition, OXPHOS activity was positively associated with the score in Digital Symbol Substitution Test (R=0,388; p=0,038).

Our pilot data show that regular exercise provides benefits to the mitochondrial function and that improvements in functional state of muscle mitochondria is linked to the better metabolic and cognitive health in seniors with mild cognitive impairment.


Bioblast editor: Kandolf G O2k-Network Lab: AT Innsbruck Oroboros, SK Bratislava Sumbalova Z


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style  Pathology: Aging;senescence 

Organism: Human  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue 


Coupling state: LEAK  Pathway: N, NS  HRR: Oxygraph-2k 


Affiliations

Nemec M(1), Maderová D(1), Krumpolec P(1), Sedliak M(2), Cvečka J(2), Tirpáková V(3), Slobodová L(4), Schön M(4), Sumbalová Z(5,6), Ukropcová B(1,2,4), Ukropec J(1)
  1. Inst Exp. Endocrinol, Biomedical Research Center, Slovak Academy Sci
  2. Fac Physical Education Sport, Comenius Univ
  3. Inst Sports Medicine Physical Education, Slovak Medical Univ
  4. Inst Pathol Physiol
  5. Pharmacobiochem Lab, Fac Medicine, Comenius Univ; Bratislava, Slovakia
  6. Daniel Swarovski Research Lab, Dept Visceral, Transplant Thoracic Surgery, Medical Univ Innsbruck, Austria
- michal.nemec@savba.sk

References and support

  1. Doerrier C, Sumbalova Z, Krumschnabel G, Hiller E, Gnaiger (2016) SUIT reference protocol for OXPHOS analysis by high-resolution respirometry. Mitochondr Physiol Network 21.06(01):1-12.  »»Bioblast link
Grant support: VEGA 2/0191/15; APVV-15-0253; SAS-NSC JRC 2013/17