A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism.
A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism.
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DOI：
10.1016/j.cmet.2018.03.015
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发表时间：
2018-05-01
期刊：
影响因子：
29
通讯作者：
Lusis AJ
中科院分区：
文献类型：
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作者：
Seldin MM;Koplev S;Rajbhandari P;Vergnes L;Rosenberg GM;Meng Y;Pan C;Phuong TMN;Gharakhanian R;Che N;Mäkinen S;Shih DM;Civelek M;Parks BW;Kim ED;Norheim F;Chella Krishnan K;Hasin-Brumshtein Y;Mehrabian M;Laakso M;Drevon CA;Koistinen HA;Tontonoz P;Reue K;Cantor RM;Björkegren JLM;Lusis AJ
通过分泌蛋白的组织间通讯已被确定为适当的生理稳态的重要机制。在这里，我们报告了一个使用小鼠参考群体的生物信息学框架，杂交小鼠多样性小组（HMDP），它集成了全球多组织表达数据和公开可用资源，以识别和功能注释组织-组织通信的新电路。我们通过表明我们可以识别负责组织间通信的已知以及新的内分泌因子来验证这种方法。我们进一步展示了这种方法的效用，通过鉴定和机制表征两个新的内分泌因子。脂肪来源的脂脂素-5被证明可以增强骨骼肌线粒体功能，肝脏分泌的Notum促进白色脂肪组织的褐化，也被称为“北京”。我们通过提供另外3种介导组织-组织相互作用的新分子的体内证据来证明该方法的一般适用性。Seldin和同事使用基于生物信息学的方法来识别新的组织间内分泌回路。利用这一资源，他们报道了两种新的内分泌因子——促进肌肉线粒体呼吸的脂肪来源的Lipocalin-5和介导脂肪组织转化的肝分泌的Notum。
Inter-tissue communication via secreted proteins has been established as a vital mechanism for proper physiologic homeostasis. Here, we report a bioinformatics framework using a mouse reference population, the Hybrid Mouse Diversity Panel (HMDP), which integrates global multi-tissue expression data and publicly available resources to identify and functionally annotate novel circuits of tissue-tissue communication. We validate this method by showing that we can identify known as well as novel endocrine factors responsible for communication between tissues. We further show the utility of this approach by identification and mechanistic characterization of two new endocrine factors. Adipose-derived Lipocalin-5 is shown to enhance skeletal muscle mitochondrial function and liver-secreted Notum promotes browning of white adipose tissue, also known as “beiging”. We demonstrate the general applicability of the method by providing in vivo evidence for 3 additional novel molecules mediating tissue-tissue interactions. Seldin and colleagues use a bioinformatics-based approach to identify new inter-tissue endocrine circuits. Using this resource, they report on two novel endocrine factors -Adipose-derived Lipocalin-5, which promotes muscle mitochondrial respiration and liver-secreted Notum, which mediates adipose tissue beiging.
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DOI：
10.1126/science.aad6970
发表时间：
2016-08-19
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franzén O;Ermel R;Cohain A;Akers NK;Di Narzo A;Talukdar HA;Foroughi-Asl H;Giambartolomei C;Fullard JF;Sukhavasi K;Köks S;Gan LM;Giannarelli C;Kovacic JC;Betsholtz C;Losic B;Michoel T;Hao K;Roussos P;Skogsberg J;Ruusalepp A;Schadt EE;Björkegren JL
通讯作者：
Björkegren JL
影响因子：
5.2
作者：
Collins S
通讯作者：
Collins S
影响因子：
4.5
作者：
Bennett BJ;Davis RC;Civelek M;Orozco L;Wu J;Qi H;Pan C;Packard RR;Eskin E;Yan M;Kirchgessner T;Wang Z;Li X;Gregory JC;Hazen SL;Gargalovic PS;Lusis AJ
通讯作者：
Lusis AJ
影响因子：
14.9
作者：
UniProt Consortium
通讯作者：
UniProt Consortium
DOI：
10.1038/nrg3575
发表时间：
2014-01
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
通讯作者：
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