Skeletal muscle myostatin mRNA expression is upregulated in aged human adults with excess adiposity but is not associated with insulin resistance and ageing.
Skeletal muscle myostatin mRNA expression is upregulated in aged human adults with excess adiposity but is not associated with insulin resistance and ageing.
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DOI：
10.1007/s11357-023-00956-6
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发表时间：
2024-04
期刊：
影响因子：
5.6
通讯作者：
Tsintzas, Kostas
中科院分区：
文献类型：
--
作者：
Wilhelmsen, Andrew;Stephens, Francis B.;Bennett, Andrew J.;Karagounis, Leonidas G.;Jones, Simon W.;Tsintzas, Kostas
肌生长抑制素负性调节骨骼肌生长，在人类肥胖中上调，并与胰岛素抵抗相关。然而，观察结果被老化所混淆，并且负责的机制尚不清楚。本研究的目的是描绘过度肥胖，胰岛素抵抗和衰老对人骨骼肌肌生长抑制素mRNA表达的影响，并使用体外模型研究致病因素。进行人体骨骼肌的体内横截面分析，以分离过度肥胖和衰老本身对肌生长抑制素表达的影响。体外研究采用人原代肌管来研究皮下脂肪组织（SAT）和骨骼肌之间的串扰以及脂质诱导的胰岛素抵抗的潜在参与。过度肥胖的老年人的骨骼肌肌生长抑制素mRNA表达高于年龄匹配的正常肥胖成年人（高2.0倍; P < 0.05），并且与维持肌肉质量的基因表达改变同时发生，但在年轻和正常肥胖的老年人之间没有差异。无论是长期暴露于肥胖的SAT分泌组，也不是急性升高的脂肪酸的可用性（诱导胰岛素抵抗）复制肥胖介导的上调肌肉生长抑制素mRNA的表达在体外。总之，骨骼肌肌生长抑制素mRNA的表达是独特的上调，在老年人过度肥胖和胰岛素抵抗，但不是由老化单独。这似乎不是由SAT分泌组或脂质诱导的胰岛素抵抗介导的。因此，骨骼肌的内在因素可能是肥胖介导的肌生长抑制素上调的原因，需要进一步的工作来建立因果关系。
Myostatin negatively regulates skeletal muscle growth and appears upregulated in human obesity and associated with insulin resistance. However, observations are confounded by ageing, and the mechanisms responsible are unknown. The aim of this study was to delineate between the effects of excess adiposity, insulin resistance and ageing on myostatin mRNA expression in human skeletal muscle and to investigate causative factors using in vitro models. An in vivo cross-sectional analysis of human skeletal muscle was undertaken to isolate effects of excess adiposity and ageing per se on myostatin expression. In vitro studies employed human primary myotubes to investigate the potential involvement of cross-talk between subcutaneous adipose tissue (SAT) and skeletal muscle, and lipid-induced insulin resistance. Skeletal muscle myostatin mRNA expression was greater in aged adults with excess adiposity than age-matched adults with normal adiposity (2.0-fold higher; P < 0.05) and occurred concurrently with altered expression of genes involved in the maintenance of muscle mass but did not differ between younger and aged adults with normal adiposity. Neither chronic exposure to obese SAT secretome nor acute elevation of fatty acid availability (which induced insulin resistance) replicated the obesity-mediated upregulation of myostatin mRNA expression in vitro. In conclusion, skeletal muscle myostatin mRNA expression is uniquely upregulated in aged adults with excess adiposity and insulin resistance but not by ageing alone. This does not appear to be mediated by the SAT secretome or by lipid-induced insulin resistance. Thus, factors intrinsic to skeletal muscle may be responsible for the obesity-mediated upregulation of myostatin, and future work to establish causality is required.
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影响因子：
4.1
作者：
Hittel DS;Axelson M;Sarna N;Shearer J;Huffman KM;Kraus WE
通讯作者：
Kraus WE
DOI：
10.1073/pnas.1525795113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Camporez, Joao-Paulo G.;Petersen, Max C.;Shulman, Gerald I.
通讯作者：
Shulman, Gerald I.
影响因子：
2.4
作者：
Dalbo, V. J.;Roberts, M. D.;Beck, D. T.
通讯作者：
Beck, D. T.
DOI：
10.1152/ajpendo.2000.279.2.e366
发表时间：
2000-08-01
影响因子：
5.1
作者：
Gallagher, D;Ruts, E;Heymsfield, SB
通讯作者：
Heymsfield, SB
肌细胞内脂质对全身脂肪氧化的相对贡献率随年龄增长而降低，但浆膜下脂质积累和胰岛素抵抗仅与超重个体有关。
影响因子：
7.7
作者：
Chee C;Shannon CE;Burns A;Selby AL;Wilkinson D;Smith K;Greenhaff PL;Stephens FB
通讯作者：
Stephens FB