mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass.
mRNA expression signatures of human skeletal muscle atrophy identify a natural compound that increases muscle mass.
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DOI：
10.1016/j.cmet.2011.03.020
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发表时间：
2011-06-08
期刊：
影响因子：
29
通讯作者：
Adams CM
中科院分区：
文献类型：
--
作者：
Kunkel SD;Suneja M;Ebert SM;Bongers KS;Fox DK;Malmberg SE;Alipour F;Shields RK;Adams CM
骨骼肌萎缩是一种常见且令人衰弱的疾病，缺乏药物治疗。为了开发一种潜在的疗法，我们鉴定了人类和小鼠肌肉中 63 种受禁食调节的 mRNA，以及人类肌肉中 29 种受禁食和脊髓损伤调节的 mRNA。我们使用这两个肌肉萎缩的无偏 mRNA 表达特征来查询连接图，该连接图挑选出熊果酸作为一种化合物，其特征与引起萎缩的应激特征相反。熊果酸是一种富含苹果的天然化合物，可以减少小鼠的肌肉萎缩并刺激肌肉肥大。它通过增强骨骼肌胰岛素/IGF-I 信号传导并抑制与萎缩相关的骨骼肌 mRNA 表达来实现这一点。重要的是，熊果酸对肌肉的影响伴随着肥胖、空腹血糖、血浆胆固醇和甘油三酯的减少。这些发现确定了肌肉萎缩和其他代谢疾病的潜在疗法。
Skeletal muscle atrophy is a common and debilitating condition that lacks a pharmacologic therapy. To develop a potential therapy, we identified 63 mRNAs that were regulated by fasting in both human and mouse muscle, and 29 mRNAs that were regulated by both fasting and spinal cord injury in human muscle. We used these two unbiased mRNA expression signatures of muscle atrophy to query the Connectivity Map, which singled out ursolic acid as a compound whose signature was opposite to those of atrophy-inducing stresses. A natural compound enriched in apples, ursolic acid reduced muscle atrophy and stimulated muscle hypertrophy in mice. It did so by enhancing skeletal muscle insulin/IGF-I signaling, and inhibiting atrophy-associated skeletal muscle mRNA expression. Importantly, ursolic acid’s effects on muscle were accompanied by reductions in adiposity, fasting blood glucose and plasma cholesterol and triglycerides. These findings identify a potential therapy for muscle atrophy and perhaps other metabolic diseases.
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