Increasing mitochondrial ATP synthesis with butyrate normalizes ADP and contractile function in metabolic heart disease.
NMR Biomed
; 33(5): e4258, 2020 05.
Article
de En
| MEDLINE
| ID: mdl-32066202
ABSTRACT
Metabolic heart disease (MHD), which is strongly associated with heart failure with preserved ejection fraction, is characterized by reduced mitochondrial energy production and contractile performance. In this study, we tested the hypothesis that an acute increase in ATP synthesis, via short chain fatty acid (butyrate) perfusion, restores contractile function in MHD. Isolated hearts of mice with MHD due to consumption of a high fat high sucrose (HFHS) diet or on a control diet (CD) for 4 months were studied using 31 P NMR spectroscopy to measure high energy phosphates and ATP synthesis rates during increased work demand. At baseline, HFHS hearts had increased ADP and decreased free energy of ATP hydrolysis (ΔG~ATP ), although contractile function was similar between the two groups. At high work demand, the ATP synthesis rate in HFHS hearts was reduced by over 50%. Unlike CD hearts, HFHS hearts did not increase contractile function at high work demand, indicating a lack of contractile reserve. However, acutely supplementing HFHS hearts with 4mM butyrate normalized ATP synthesis, ADP, ΔG~ATP and contractile reserve. Thus, acute reversal of depressed mitochondrial ATP production improves contractile dysfunction in MHD. These findings suggest that energy starvation may be a reversible cause of myocardial dysfunction in MHD, and opens new therapeutic opportunities.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Butyrates
/
Maladies cardiovasculaires
/
ADP
/
Adénosine triphosphate
/
Maladies métaboliques
/
Mitochondries du myocarde
/
Contraction myocardique
Limites:
Animals
Langue:
En
Journal:
NMR Biomed
Sujet du journal:
DIAGNOSTICO POR IMAGEM
/
MEDICINA NUCLEAR
Année:
2020
Type de document:
Article