Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training.
Genomics and transcriptomics landscapes associated to changes in insulin sensitivity in response to endurance exercise training.
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耐力运动训练后胰岛素敏感性变化的基因组学和转录组学研究
DOI：
10.1038/s41598-021-98792-1
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发表时间：
2021-12-02
影响因子：
4.6
通讯作者：
Falciani F
中科院分区：
文献类型：
--
作者：
Takeshita LY;Davidsen PK;Herbert JM;Antczak P;Hesselink MKC;Schrauwen P;Weisnagel SJ;Robbins JM;Gerszten RE;Ghosh S;Sarzynski MA;Bouchard C;Falciani F
尽管很好地坚持了有监督的耐力运动训练（EET），但有些人的外周胰岛素敏感性没有或只有很少的改善。这一现象背后的遗传和分子机制目前尚不清楚。通过研究与健康志愿者胰岛素敏感性指数（Si）基线和运动诱导变化（∆）相关的全基因组变异，我们已经确定了新的候选基因，其小鼠敲除表型与Si的致病作用一致。功能基因组和转录组谱的综合分析表明，遗传变异对基线Si和∆Si有总体影响，主要围绕胆碱能信号传导，包括下游钙和趋化因子信号传导。钙调控的MEF2A转录因子是驱动∆Si相关转录特征的最具统计学意义的候选因子，这进一步加强了钙信号在EET介导的Si反应中的相关性。
Despite good adherence to supervised endurance exercise training (EET), some individuals experience no or little improvement in peripheral insulin sensitivity. The genetic and molecular mechanisms underlying this phenomenon are currently not understood. By investigating genome-wide variants associated with baseline and exercise-induced changes (∆) in insulin sensitivity index (Si) in healthy volunteers, we have identified novel candidate genes whose mouse knockouts phenotypes were consistent with a causative effect on Si. An integrative analysis of functional genomic and transcriptomic profiles suggests genetic variants have an aggregate effect on baseline Si and ∆Si, focused around cholinergic signalling, including downstream calcium and chemokine signalling. The identification of calcium regulated MEF2A transcription factor as the most statistically significant candidate driving the transcriptional signature associated to ∆Si further strengthens the relevance of calcium signalling in EET mediated Si response.
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影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
影响因子：
158.5
作者：
Knowler, WC;Barrett-Connor, E;Nathan, DM
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遗传对人体组织基因表达的影响。
影响因子：
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作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
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Montgomery SB
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Boston, Ray C;Stefanovski, Darko;Bergman, Richard N
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Bergman, Richard N
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14.9
作者：
Buniello, Annalisa;MacArthur, Jacqueline A. L.;Parkinson, Helen
通讯作者：
Parkinson, Helen