Adiponectin, the most abundant adipokine in the circulation, plays an important role in maintaining cardiovascular health in both rodents and humans. Previous work from our lab has shown that mice lacking adiponectin fail to gain improvements in microvascular function and cardiac function—including ejection fraction, isovolumetric contraction time, and isovolumetric relaxation time—after exercise training. However, the impact of adiponectin depletion on sarcomere mechanics remains poorly defined. To address this, we studied skinned papillary muscle preparations from wild-type (WT) and adiponectin knockout (AdipoKO) mice and measured steady-state isometric force, crossbridge kinetics ( k TR ), sinusoidal stiffness (SS), and the proportion of myosin heads in the super-relaxed state (SRX). In WT mice, exercise training increased maximal steady-state isometric force and SS, and lowered myofilament Ca 2+ sensitivity. In contrast, exercise diminished steady-state isometric force and SS, and increased myofilament Ca 2+ sensitivity in AdipoKO hearts. Across both sedentary and trained groups, AdipoKO fibers exhibited significantly faster k TR at physiological Ca 2+ levels than WT, indicating faster crossbridge kinetics, while SRX levels (measured biochemically using mantATP-chase assay) were unchanged between all groups. These results suggest that chronic adiponectin deficiency accelerates crossbridge turnover and reduces isometric force levels in skinned cardiac muscle. These fiber-level changes are consistent with the absence of exercise-induced improvements in systolic function observed in vivo in AdipoKO mice. Together, these findings identify adiponectin as a critical regulator of myofilament efficiency and highlight how its loss shifts exercise from a beneficial adaptation to a maladaptive stress on the cardiovascular system.
Medarev et al. (Sun,) studied this question.