Satellite cell content and muscle regeneration in a mouse model of NAFLD
Satellite cell content and muscle regeneration in a mouse model of NAFLD
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NAFLD 小鼠模型中的卫星细胞含量和肌肉再生
DOI：
10.1016/j.nut.2021.111570
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发表时间：
2022
期刊：
影响因子：
4.4
通讯作者：
Yanaka N.
中科院分区：
文献类型：
--
作者：
Saliu TP;Kumrungsee T;Mitsumoto K;Chen S;Yanaka N.
目的肌肉萎缩是非酒精性脂肪性肝病(NAFLD)患者的常见并发症。本研究旨在探讨NAFLD对星形细胞(SC)含量和骨骼肌修复的影响。方法雄性CD-1小鼠以低胆碱饲料喂养4wk建立NAFLD模型。结果与对照组相比，NAFLD组小鼠指长伸肌和胫前肌中Pax7+SCs的总数明显减少，其中SC池的耗竭可能影响肌肉的再生，再生的肌纤维较小。重要的是，我们发现NAFLD显著削弱了干细胞的分化能力，表现为表达肌源性标志物MyoD的干细胞数量减少。结论非酒精性脂肪性肝病小鼠骨骼肌中SC含量减少可能与促炎细胞因子(肿瘤坏死因子α)和氧化应激标志物NADPH氧化酶-2[α]上调有关。因此，保存肌肉SC池是减少NAFLD相关肌肉损耗的潜在治疗策略。
ObjectivesMuscle wasting is a common complication in patients with nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effect of NAFLD on satellite cell (SC) content and skeletal muscle repair.MethodsMale CD-1 mice fed a choline-deficient diet for 4 wk were used as an NAFLD model. We performed histologic and mRNA expression analyses, immunochemical staining with single muscle fibers to assess the effect of NAFLD on muscle Pax7+ SCs, and muscle regeneration by intramuscular injection of cardiotoxin.ResultsWe found that the total number of Pax7+ SCs in the extensor digitorum longus and tibialis anterior muscles of mice with NAFLD was significantly decreased when compared with that in the control group, in which the depletion of the SC pool possibly impaired muscle regeneration, as evidenced by the smaller size of the regenerating myofibers. Importantly, we found that NAFLD significantly impaired the differentiation ability of SCs, as shown by a decreased number of SCs expressing a myogenic marker, MyoD. Finally, this study indicated that molecular mechanisms underlying a decline in SC numbers may be attributed to the upregulation of proinflammatory cytokines (tumor necrosis factor α [TNFα]) and an oxidative stress marker (NADPH oxidase-2 [NOX2\) in mice with NAFLD.ConclusionsThe findings demonstrate that a decrease in SC content in the skeletal muscle is an important factor that contributes to muscle wasting in NAFLD. Thus, preservation of the muscle SC pool is a potential therapeutic strategy to reduce NAFLD-associated muscle wasting.