Abou-Samra Michel, Dubuisson Nicolas, Marino Alice, Selvais Camille M, Romain Versele, Davis-López de Carrizosa Maria A, Noel Laurence, Beauloye Christophe, Brichard Sonia M, Horman Sandrine
Endocrinology, Diabetes and Nutrition Unit, Institute of Experimental and Clinical Research (IREC), Medical Sector, Université Catholique de Louvain (UCLouvain), Avenue Hippocrate 55, 1200 Brussels, Belgium.
Neuromuscular Reference Center, Department of Neurology, Cliniques Universitaires Saint-Luc, Avenue Hippocrate 10, 1200 Brussels, Belgium.
Antioxidants (Basel). 2024 Dec 18;13(12):1551. doi: 10.3390/antiox13121551.
Adiponectin (ApN) is a hormone with potent effects on various tissues. We previously demonstrated its ability to counteract Duchenne muscular dystrophy (DMD), a severe muscle disorder. However, its therapeutic use is limited. AdipoRon, an orally active ApN mimic, offers a promising alternative. While cardiomyopathy is the primary cause of mortality in DMD, the effects of ApN or AdipoRon on dystrophic hearts have not been investigated. Our recent findings demonstrated the significant protective effects of AdipoRon on dystrophic skeletal muscle. In this study, we investigated whether AdipoRon effects could be extended to dystrophic hearts. As cardiomyopathy develops late in mdx mice (DMD mouse model), 14-month-old mdx mice were orally treated for two months with AdipoRon at a dose of 50 mg/kg/day and then compared with untreated mdx and wild-type (WT) controls. Echocardiography revealed cardiac dysfunction and ventricular hypertrophy in mdx mice, which were fully reversed in AdipoRon-treated mice. AdipoRon also reduced markers of cardiac inflammation, oxidative stress, hypertrophy, and fibrosis while enhancing mitochondrial biogenesis via ApN receptor-1 and CAMKK2/AMPK pathways. Remarkably, treated mice also showed improved skeletal muscle strength and endurance. By offering protection to both cardiac and skeletal muscles, AdipoRon holds potential as a comprehensive therapeutic strategy for better managing DMD.
脂联素（ApN）是一种对多种组织具有强大作用的激素。我们之前证明了它具有对抗杜氏肌营养不良症（DMD，一种严重的肌肉疾病）的能力。然而，其治疗用途有限。AdipoRon是一种口服活性ApN模拟物，提供了一种有前景的替代方案。虽然心肌病是DMD患者死亡的主要原因，但ApN或AdipoRon对营养不良心脏的影响尚未得到研究。我们最近的研究结果表明AdipoRon对营养不良的骨骼肌具有显著的保护作用。在本研究中，我们调查了AdipoRon的作用是否可以扩展到营养不良的心脏。由于心肌病在mdx小鼠（DMD小鼠模型）中发展较晚，14月龄的mdx小鼠每天以50 mg/kg的剂量口服AdipoRon治疗两个月，然后与未治疗的mdx小鼠和野生型（WT）对照进行比较。超声心动图显示mdx小鼠存在心脏功能障碍和心室肥大，而在接受AdipoRon治疗的小鼠中这些情况完全得到逆转。AdipoRon还降低了心脏炎症、氧化应激、肥大和纤维化的标志物，同时通过ApN受体-1和CAMKK2/AMPK途径增强线粒体生物合成。值得注意的是，接受治疗的小鼠还表现出骨骼肌力量和耐力的改善。通过对心脏和骨骼肌都提供保护，AdipoRon有望成为更好管理DMD的综合治疗策略。
