The absolute value of free energy of ATP hydrolysis, |ΔGATP |, was lower in HFHS hearts at all levels of work demand. Perfusion with butyrate prevented the detrimental decrease in |Δ GATP| (A). The lack in contractile reserve is revealed when |Δ GATP |is plotted against the work performed (RPP), where, at the highest workloads, the |Δ GATP | fell below the free energy required for sarcoplasmic reticulum ATPase (SERCA) function. This deficit in contractile reserve was fully restored to normal values upon perfusion with butyrate even at the highest work demand (B), n=6–7; **p<0.01.