Linc-RAM is a metabolic regulator maintaining whole-body energy homeostasis in mice.
Linc-RAM is a metabolic regulator maintaining whole-body energy homeostasis in mice.
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Linc-RAM 是一种维持小鼠全身能量稳态的代谢调节剂
DOI：
10.3724/abbs.2022170
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发表时间：
2022-11-25
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
已知长链非编码RNA（lncRNA）在调节细胞命运、细胞分化、器官形成和疾病中具有深远的功能，但其在控制细胞代谢和全身代谢稳态中的生理作用尚不清楚。我们以前确定了骨骼肌特异性的长基因间非编码RNA（linc-RNA）的肌肉发生，Linc-RAM，这增强了肌肉细胞分化过程中的发展和再生的激活剂。在这里，我们报告，Linc-RAM发挥调节骨骼肌代谢和基础代谢率，以维持全身代谢稳态的生理功能。我们首先证明，Linc-RAM优先表达在II型丰富的糖酵解肌纤维，其中其水平是60倍以上的分化肌管相比。一致的是，在小鼠中Linc-RAM基因的遗传缺失增加了编码肌球蛋白重链的氧化纤维版本的基因的表达水平，并降低了编码糖酵解代谢的限速酶的基因的表达水平。在生理学上，Linc-RAM基因敲除小鼠与野生型同窝小鼠相比，表现出更高的基础代谢率、更高的胰岛素敏感性和更少的脂肪沉积。总之，我们的研究结果表明，Linc-RAM是骨骼肌代谢的代谢调节剂，并可能代表预防和/或治疗代谢性疾病，包括肥胖症的潜在药物靶点。
Long noncoding RNAs (lncRNAs) are known to have profound functions in regulating cell fate specification, cell differentiation, organogenesis, and disease, but their physiological roles in controlling cellular metabolism and whole-body metabolic homeostasis are less well understood. We previously identified a skeletal muscle-specific long intergenic noncoding RNA (linc-RNA) activator of myogenesis, Linc-RAM, which enhances muscle cell differentiation during development and regeneration. Here, we report that Linc-RAM exerts a physiological function in regulating skeletal muscle metabolism and the basal metabolic rate to maintain whole-body metabolic homeostasis. We first demonstrate that Linc-RAM is preferentially expressed in type-II enriched glycolytic myofibers, in which its level is more than 60-fold higher compared to that in differentiated myotubes. Consistently, genetic deletion of the Linc-RAM gene in mice increases the expression levels of genes encoding oxidative fiber versions of myosin heavy chains and decreases those of genes encoding rate-limiting enzymes for glycolytic metabolism. Physiologically, Linc-RAM-knockout mice exhibit a higher basal metabolic rate, elevated insulin sensitivity and reduced fat deposition compared to their wild-type littermates. Together, our findings indicate that Linc-RAM is a metabolic regulator of skeletal muscle metabolism and may represent a potential pharmaceutical target for preventing and/or treating metabolic diseases, including obesity.
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影响因子：
16
作者：
Legnini, Ivano;Morlando, Mariangela;Mangiavacchi, Arianna;Fatica, Alessandro;Bozzoni, Irene
通讯作者：
Bozzoni, Irene
影响因子：
29
作者：
Park MK;Zhang L;Min KW;Cho JH;Yeh CC;Moon H;Hormaechea-Agulla D;Mun H;Ko S;Lee JW;Jathar S;Smith AS;Yao Y;Giang NT;Vu HH;Yan VC;Bridges MC;Kourtidis A;Muller F;Chang JH;Song SJ;Nakagawa S;Hirose T;Yoon JH;Song MS
通讯作者：
Song MS
肌肉液脂肪信号轴对于自适应脂肪重塑的中心控制至关重要。
影响因子：
16.6
作者：
Shimizu, Noriaki;Maruyama, Takako;Yoshikawa, Noritada;Matsumiya, Ryo;Ma, Yanxia;Ito, Naoki;Tasaka, Yuki;Kuribara-Souta, Akiko;Miyata, Keishi;Oike, Yuichi;Berger, Stefan;Schuetz, Guenther;Takeda, Shin'ichi;Tanaka, Hirotoshi
通讯作者：
Tanaka, Hirotoshi
影响因子：
56.9
作者：
Bocchi, Vittoria Dickinson;Conforti, Paola;Cattaneo, Elena
通讯作者：
Cattaneo, Elena
影响因子：
3.4
作者：
Macharia, Raymond;Otto, Anthony;Patel, Ketan
通讯作者：
Patel, Ketan