Key result
Aerobic exercise improves diastolic function and reduces neuronal injury in pre-clinical HFpEF.
Its licence doesn't allow us to show a copy here.
Why the study?
Heart failure with preserved ejection fraction (HFpEF) is associated with sympathetic overactivation and brain-heart axis dysregulation involving ALCAT1, but the roles of aerobic exercise and ALCAT1 in this process are unclear.
Does aerobic exercise and ALCAT1 suppression improve cardiac diastolic function and reduce neuroinflammation in HFpEF models?
Does aerobic exercise and ALCAT1 suppression improve cardiac diastolic function and reduce neuroinflammation in HFpEF models?
Aerobic exercise improves diastolic function and reduces sympathetic overactivation in HFpEF mice by modulating ALCAT1 and GDF5 in critical cardiovascular regulatory centers.
May support ALCAT1 as adjunct to exercise in HFpEF; leaves open clinical translation of central mechanisms.
BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is commonly accompanied by sympathetic overactivation, contributing to poor patient prognosis. The paraventricular nucleus (PVN) and nucleus tractus solitarius (NTS) are critical cardiovascular regulatory centers. Pathological cardiolipin (CL) remodeling catalyzed by Acyl-CoA:lysocardiolipin acyltransferase 1 (ALCAT1) exacerbates disease progression. This study aims to elucidate the roles of aerobic exercise and ALCAT1 in modulating brain-heart axis dysregulation in HFpEF. METHODS AND RESULTS: We employed wild-type (WT) and Alcat1 knockout mice to establish an HFpEF model, followed by aerobic exercise. Neuroinflammatory model was established to investigate the role of ALCAT1 in neuroinflammation. Underlying mechanisms were explored in HT22 cells. In HFpEF mice, aerobic exercise suppressed ALCAT1 and up-regulated growth differentiation factor 5 (GDF5) in the PVN and NTS, reduced pro-inflammatory cytokines, enhanced antioxidant enzyme activities, decreased oxidative stress markers, and attenuated neuronal structural damage and hyperactivation. These central improvements were accompanied by attenuated cardiac sympathetic overactivation, lowered blood pressure, and improved diastolic function. The important role of ALCAT1 was further supported, as its genetic knockout conferred significant protection in both HFpEF and neuroinflammatory models. In HT22 cells, GDF5 suppressed the LPS-induced ALCAT1 up-regulation and ameliorated cellular injury. CONCLUSION: ALCAT1 is an important contributor to neuronal injury. Aerobic exercise suppresses ALCAT1 and up-regulates GDF5, ameliorating neuronal injury and improving diastolic function in HFpEF mice. Mechanistically, ALCAT1 and GDF5 are reciprocally regulated, which may contribute to the protective effects of aerobic exercise against HFpEF. These findings suggest ALCAT1 as a potential molecular target for exercise-based HFpEF therapy.
No takes yet. Share an insight, caveat, or question.
Zhao et al. (2026) studied Heart failure with preserved ejection fraction (HFpEF). Aerobic exercise vs. No exercise / Wild-type HFpEF model was evaluated. Aerobic exercise suppressed ALCAT1, up-regulated GDF5, and ameliorated neuronal injury and diastolic function in a mouse model of HFpEF.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: