Heart Center Dresden, Laboratory of Molecular and Experimental Cardiology, TU Dresden, 01307 Dresden, Germany.
Department of Anatomy, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo 05508000, Brazil.
Cells. 2024 Mar 13;13(6):502. doi: 10.3390/cells13060502.
Heart failure with preserved ejection fraction (HFpEF) is associated with exercise intolerance due to alterations in the skeletal muscle (SKM). Leucine supplementation is known to alter the anabolic/catabolic balance and to improve mitochondrial function. Thus, we investigated the effect of leucine supplementation in both a primary and a secondary prevention approach on SKM function and factors modulating muscle function in an established HFpEF rat model. Female ZSF1 obese rats were randomized to an untreated, a primary prevention, and a secondary prevention group. For primary prevention, leucine supplementation was started before the onset of HFpEF (8 weeks of age) and for secondary prevention, leucine supplementation was started after the onset of HFpEF (20 weeks of age). SKM function was assessed at an age of 32 weeks, and SKM tissue was collected for the assessment of mitochondrial function and histological and molecular analyses. Leucine supplementation prevented the development of SKM dysfunction whereas it could not reverse it. In the primary prevention group, mitochondrial function improved and higher expressions of mitofilin, Mfn-2, Fis1, and miCK were evident in SKM. The expression of UCP3 was reduced whereas the mitochondrial content and markers for catabolism (MuRF1, MAFBx), muscle cross-sectional area, and SKM mass did not change. Our data show that leucine supplementation prevented the development of skeletal muscle dysfunction in a rat model of HFpEF, which may be mediated by improving mitochondrial function through modulating energy transfer.
射血分数保留型心力衰竭（HFpEF）与骨骼肌（SKM）改变导致的运动不耐受有关。亮氨酸补充已知可改变合成代谢/分解代谢平衡并改善线粒体功能。因此，我们研究了亮氨酸补充在原发性和二级预防方法中对 SKM 功能以及调节肌肉功能的因素的影响，在已建立的 HFpEF 大鼠模型中。雌性 ZSF1 肥胖大鼠随机分为未治疗组、原发性预防组和二级预防组。对于原发性预防，亮氨酸补充在 HFpEF 发作前（8 周龄）开始，对于二级预防，亮氨酸补充在 HFpEF 发作后（20 周龄）开始。在 32 周龄时评估 SKM 功能，并收集 SKM 组织以评估线粒体功能和组织学及分子分析。亮氨酸补充可预防 SKM 功能障碍的发展，但不能逆转它。在原发性预防组中，线粒体功能改善，SKM 中可见肌联蛋白、Mfn-2、Fis1 和 miCK 的表达增加。UCP3 的表达减少，而线粒体含量和分解代谢标志物（MuRF1、MAFBx）、肌肉横截面积和 SKM 质量没有变化。我们的数据表明，亮氨酸补充可预防 HFpEF 大鼠模型中 SKM 功能障碍的发展，这可能是通过调节能量传递来改善线粒体功能介导的。
