Retinoic Acid Receptor Agonists Suppress Muscle Fatty Infiltration in Mice
Retinoic Acid Receptor Agonists Suppress Muscle Fatty Infiltration in Mice
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DOI：
10.1177/0363546520984122
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发表时间：
2021-02-01
影响因子：
4.8
通讯作者：
Horiuchi, Keisuke
中科院分区：
文献类型：
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作者：
Shirasawa, Hideyuki;Matsumura, Noboru;Horiuchi, Keisuke
背景：脂肪组织浸润到骨骼肌，一种被称为肌肉脂肪浸润或脂肪变性的状况，被认为是一种不可逆的事件，显著损害骨骼肌的运动功能。目的：研究维甲酸受体（RAR）激动剂在体外抑制纤维脂肪生成祖细胞（FAP）的脂肪生成分化和小鼠肩袖撕裂后脂肪浸润的作用。研究设计：对照实验室研究。方法：将从小鼠骨骼肌分离的FAP在脂肪生成分化培养基中培养，存在或不存在RAR激动剂。在细胞培养结束时，通过基因表达分析和油红O染色评估成脂分化。脂肪浸润的小鼠模型包括切除肩袖、去除肱骨头和冈上肌去神经支配，用于诱导冈上肌脂肪浸润。在手术后，小鼠口服或肌内施用RAR激动剂。结果：RAR受体激动剂能有效抑制FAPs的成脂分化。口服和肌肉注射RAR激动剂可抑制肩袖撕裂后小鼠肌肉脂肪浸润的发展。与此一致，我们发现肌内脂肪细胞的数量显著减少，成脂标志物的表达受到抑制。RAR受体激动剂也增加了胶原蛋白的转录本的表达，然而，胶原组织的积累是不明显的组织学在本model.Conclusion：肌肉脂肪浸润可以减轻RAR受体激动剂通过抑制脂肪的分化FAPs。结果还表明，RAR激动剂是治疗有肌肉脂肪浸润风险的患者的潜在治疗药物。RAR激动剂增加胶原转录物表达的后果需要澄清。
Background:The infiltration of fat tissue into skeletal muscle, a condition referred to as muscle fatty infiltration or fatty degeneration, is regarded as an irreversible event that significantly compromises the motor function of skeletal muscle.Purpose:To investigate the effect of retinoic acid receptor (RAR) agonists in suppressing the adipogenic differentiation of fibroadipogenic progenitors (FAPs) in vitro and fatty infiltration after rotator cuff tear in mice.Study Design:Controlled laboratory study.Methods:FAPs isolated from mouse skeletal muscle were cultured in adipogenic differentiation medium in the presence or absence of an RAR agonist. At the end of cell culture, adipogenic differentiation was evaluated by gene expression analysis and oil red O staining. A mouse model of fatty infiltration-which includes the resection of the rotator cuff, removal of the humeral head, and denervation the supraspinatus muscle-was used to induce fatty infiltration in the supraspinatus muscle. The mice were orally or intramuscularly administered with an RAR agonist after the surgery. Muscle fatty infiltration was evaluated by histology and gene expression analysis.Results:RAR agonists effectively inhibited the adipogenic differentiation of FAPs in vitro. Oral and intramuscular administration of RAR agonists suppressed the development of muscle fatty infiltration in the mice after rotator cuff tear. In accordance, we found a significant decrease in the number of intramuscular fat cells and suppressed expression in adipogenic markers. RAR agonists also increased the expression of the transcripts for collagens; however, an accumulation of collagenous tissues was not histologically evident in the present model.Conclusion:Muscle fatty infiltration can be alleviated by RAR agonists through suppressing the adipogenic differentiation of FAPs. The results also suggest that RAR agonists are potential therapeutic agents for treating patients who are at risk of developing muscle fatty infiltration. The consequence of the increased expression of collagen transcripts by RAR agonists needs to be clarified.