Alvarez-Chávez Ana Luisa, De Los Santos Sergio, Coral-Vázquez Ramón Mauricio, Reyes-Castro Luis Antonio, Zambrano Elena, Canto Patricia
Obesity Research Unity, Medicine Faculty, Mexico Autonomous National University, Mexico City, México.
Clinical Research Subdirection, Research Direction, National Institute of Medical Sciences and Nutrition "Salvador Zubirán", Mexico City, México.
Cell Biochem Biophys. 2025 Mar 15. doi: 10.1007/s12013-025-01690-w.
We determine whether the offspring of obese mothers and a postnatal high-fat diet (HFD) modify protein levels related to muscle synthesis (p70S6K-alpha) or atrophy (Murf and MAFbx), and if the administration of (-)-epicatechin (Epi) can modify these alterations. We hypothesized that the ubiquitin ligases Murf and MAFbx would be increased in the obesogenic context, either by in utero obesogenic environment or by a postnatal high-fat diet, while the p70S6K-alpha kinase and its activation might be decreased. Eight groups of six male Wistar offspring formed eight experimental groups: control (C), control fed with HFD (CHFD), maternal obesity (MO), maternal obesity fed with HFD (MOHFD), and the groups with Epi intervention: C+Epi long, CHFD+Epi long, MO+Epi long and MOHFD+Epi long. By Western blot, we evaluated the Epi effect on the Murf, MAFbx, and p70S6K-alpha proteins in gastrocnemius and soleus tissues. The Murf level increased 2.59-fold in CHFD vs C group and 2.62-fold for MOHFD vs C group (p = 0.049 and p = 0.048, respectively) in gastrocnemius tissue. In soleus tissue, we observed an increase of MAFbx (1.52-fold) for the MOHFD group versus the C group (p = 0.049). Epi treatment did not modify any protein expression. In conclusion, we found an increase in the Murf1 protein levels in gastrocnemius tissue of the direct model of obesity; as well, we observed an increase of the Murf1 in gastrocnemius and of the MAFbx in soleus muscles in the group of rats obese by programming and fed postnatally with a high-fat diet (doble stimulus). In addition, since obesity could cause muscle atrophy, which results in impaired muscle function, it would be relevant in future research to evaluate these signaling pathways in animals of different ages in order to search for markers of the progression of diseases such as sarcopenia obesity.
我们确定肥胖母亲的后代及产后高脂饮食（HFD）是否会改变与肌肉合成相关的蛋白水平（p70S6K-α）或萎缩相关蛋白水平（Murf和MAFbx），以及给予（-）-表儿茶素（Epi）是否能改变这些变化。我们假设，在致肥胖环境中，无论是子宫内的致肥胖环境还是产后高脂饮食，泛素连接酶Murf和MAFbx都会增加，而p70S6K-α激酶及其活性可能会降低。八组每组六只雄性Wistar后代组成了八个实验组：对照组（C）、喂食HFD的对照组（CHFD）、母体肥胖组（MO）、母体肥胖且喂食HFD组（MOHFD），以及接受Epi干预的组：C+Epi长期组、CHFD+Epi长期组、MO+Epi长期组和MOHFD+Epi长期组。通过蛋白质印迹法，我们评估了Epi对腓肠肌和比目鱼肌组织中Murf、MAFbx和p70S6K-α蛋白的影响。在腓肠肌组织中，CHFD组与C组相比，Murf水平增加了2.59倍，MOHFD组与C组相比增加了2.62倍（分别为p = 0.049和p = 0.048）。在比目鱼肌组织中，我们观察到MOHFD组的MAFbx增加（1.52倍），与C组相比（p = 0.049）。Epi处理未改变任何蛋白表达。总之，我们发现肥胖直接模型的腓肠肌组织中Murf1蛋白水平增加；同样，在通过编程致肥胖并在产后喂食高脂饮食的大鼠组（双重刺激）中，我们观察到腓肠肌中Murf1增加，比目鱼肌中MAFbx增加。此外，由于肥胖可能导致肌肉萎缩，进而导致肌肉功能受损，在未来研究中评估不同年龄动物的这些信号通路，以寻找诸如肥胖症肌肉减少症等疾病进展的标志物将具有重要意义。
