RNA sequencing reveals a slow to fast muscle fiber type transition after olanzapine infusion in rats.
RNA sequencing reveals a slow to fast muscle fiber type transition after olanzapine infusion in rats.
复制标题
DOI：
10.1371/journal.pone.0123966
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kawasawa YI
中科院分区：
文献类型：
--
作者：
Lynch CJ;Xu Y;Hajnal A;Salzberg AC;Kawasawa YI
第二代抗精神病药物（SGAs），如奥氮平，表现出急性代谢副作用，导致代谢不灵活，高血糖，肥胖和糖尿病。了解SGAs如何影响骨骼肌转录组可以阐明减轻这些副作用的方法。雄性Sprague-Dawley大鼠静脉注射小鼠或奥氮平24小时，剂量导致轻度高血糖。在腓肠肌上进行RNA-Seq，然后使用大鼠基因组组装5.0对数据进行比对。奥氮平改变了26407个基因中的1347个基因的表达。编码骨骼肌纤维型特异性肌聚体、离子通道、糖酵解、O2-和Ca2+处理、TCA循环、血管化和脂质氧化蛋白和途径以及NADH穿梭体和LDH亚型的基因受到影响。生物信息学分析表明，奥氮平降低了较慢和更多氧化纤维类型基因（如1型）的表达，而上调了糖酵解能力最强和代谢灵活性最低的快肌纤维类型IIb的表达。蛋白质转换基因，必需的转变，也上调。潜在的上游监管机构也被确定。奥氮平似乎能迅速影响肌肉转录组，使其转变为快速糖酵解纤维类型。这种纤维类型比慢肌更容易萎缩，这种转变在慢性代谢疾病中观察到。因此，这些影响可能导致机体成分的改变和奥氮平引起的代谢性疾病。这涉及到一种潜在的干预策略，因为有氧运动，与阻力运动相反，可以反对这种缓慢到快速的纤维转换。
Second generation antipsychotics (SGAs), like olanzapine, exhibit acute metabolic side effects leading to metabolic inflexibility, hyperglycemia, adiposity and diabetes. Understanding how SGAs affect the skeletal muscle transcriptome could elucidate approaches for mitigating these side effects. Male Sprague-Dawley rats were infused intravenously with vehicle or olanzapine for 24h using a dose leading to a mild hyperglycemia. RNA-Seq was performed on gastrocnemius muscle, followed by alignment of the data with the Rat Genome Assembly 5.0. Olanzapine altered expression of 1347 out of 26407 genes. Genes encoding skeletal muscle fiber-type specific sarcomeric, ion channel, glycolytic, O2- and Ca2+-handling, TCA cycle, vascularization and lipid oxidation proteins and pathways, along with NADH shuttles and LDH isoforms were affected. Bioinformatics analyses indicate that olanzapine decreased the expression of slower and more oxidative fiber type genes (e.g., type 1), while up regulating those for the most glycolytic and least metabolically flexible, fast twitch fiber type, IIb. Protein turnover genes, necessary to bring about transition, were also up regulated. Potential upstream regulators were also identified. Olanzapine appears to be rapidly affecting the muscle transcriptome to bring about a change to a fast-glycolytic fiber type. Such fiber types are more susceptible than slow muscle to atrophy, and such transitions are observed in chronic metabolic diseases. Thus these effects could contribute to the altered body composition and metabolic disease olanzapine causes. A potential interventional strategy is implicated because aerobic exercise, in contrast to resistance exercise, can oppose such slow to fast fiber transitions.
登录
查看更多内容
影响因子：
--
作者：
Fujita N;Nagatomo F;Murakami S;Kondo H;Ishihara A;Fujino H
通讯作者：
Fujino H
影响因子：
8.8
作者：
Fertuzinhos S;Li M;Kawasawa YI;Ivic V;Franjic D;Singh D;Crair M;Sestan N
通讯作者：
Sestan N
影响因子：
3.7
作者：
Albaugh VL;Singareddy R;Mauger D;Lynch CJ
通讯作者：
Lynch CJ
影响因子：
5.4
作者：
Chen, Li-Na;Lyu, Juan;Wang, Bing
通讯作者：
Wang, Bing
影响因子：
7.7
作者：
Arikawa, Emi;Ma, Ronald C. W.;King, George L.
通讯作者：
King, George L.