Skeletal muscle mitochondrial inertia is associated with carnitine acetyltransferase activity and physical function in humans

Rodrigo F. Mancilla, Lucas Lindeboom, Lotte Grevendonk, Joris Hoeks, Tim R. Koves, Deborah M. Muoio, Patrick Schrauwen, Vera Schrauwen-Hinderling, Matthijs K.C. Hesselink

Risultato della ricercapeer review

7 Citazioni (Scopus)

Abstract

BACKGROUND. At the onset of exercise, the speed at which phosphocreatine (PCr) decreases toward a new steady state (PCr on-kinetics) reflects the readiness to activate mitochondrial ATP synthesis, which is secondary to Acetyl-CoA availability in skeletal muscle. We hypothesized that PCr on-kinetics are slower in metabolically compromised and older individuals and are associated with low carnitine acetyltransferase (CrAT) protein activity and compromised physical function. METHODS. We applied 31P-magnetic resonance spectroscopy (31P-MRS) to assess PCr on-kinetics in 2 cohorts of volunteers. Cohort 1 included patients who had type 2 diabetes, were obese, were lean trained (VO2max > 55 mL/kg/min), and were lean untrained (VO2max < 45 mL/kg/min). Cohort 2 included young (20–30 years) and older (65–80 years) individuals with normal physical activity and older, trained individuals. Previous results of CrAT protein activity and acetylcarnitine content in muscle tissue were used to explore the underlying mechanisms of PCr on-kinetics, along with various markers of physical function. RESULTS. PCr on-kinetics were significantly slower in metabolically compromised and older individuals (indicating mitochondrial inertia) as compared with young and older trained volunteers, regardless of in vivo skeletal muscle oxidative capacity (P < 0.001). Mitochondrial inertia correlated with reduced CrAT protein activity, low acetylcarnitine content, and functional outcomes (P < 0.001). CONCLUSION. PCr on-kinetics are significantly slower in metabolically compromised and older individuals with normal physical activity compared with young and older trained individuals, regardless of in vivo skeletal muscle oxidative capacity, indicating greater mitochondrial inertia. Thus, PCr on-kinetics are a currently unexplored signature of skeletal muscle mitochondrial metabolism, tightly linked to functional outcomes. Skeletal muscle mitochondrial inertia might emerge as a target of intervention to improve physical function. TRIAL REGISTRATION. NCT01298375 and NCT03666013 (clinicaltrials.gov).

Lingua originaleEnglish
Numero di articoloe163855
RivistaJCI Insight
Volume8
Numero di pubblicazione1
DOI
Stato di pubblicazionePublished - 10 gen 2023
Pubblicato esternamente

Fingerprint

Entra nei temi di ricerca di 'Skeletal muscle mitochondrial inertia is associated with carnitine acetyltransferase activity and physical function in humans'. Insieme formano una fingerprint unica.

Cita questo