| Literature DB >> 29719227 |
Marcus M Seldin1, Simon Koplev2, Prashant Rajbhandari3, Laurent Vergnes4, Gregory M Rosenberg1, Yonghong Meng1, Calvin Pan5, Thuy M N Phuong1, Raffi Gharakhanian1, Nam Che1, Selina Mäkinen6, Diana M Shih1, Mete Civelek7, Brian W Parks8, Eric D Kim1, Frode Norheim9, Karthickeyan Chella Krishnan1, Yehudit Hasin-Brumshtein1, Margarete Mehrabian1, Markku Laakso10, Christian A Drevon9, Heikki A Koistinen6, Peter Tontonoz3, Karen Reue4, Rita M Cantor4, Johan L M Björkegren2, Aldons J Lusis11.
Abstract
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 three additional novel molecules mediating tissue-tissue interactions.Entities:
Keywords: Lipocalin-5; Notum; SPARC-related modular calcium binding 1; adipocyte beiging; cross-tissue communication; endocrine; inter-alpha-trypsin inhibitor heavy chain H5; mitochondria; pro-platelet basic protein; secreted peptides; skeletal muscle respiration
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Year: 2018 PMID： 29719227 PMCID： PMC5935137 DOI： 10.1016/j.cmet.2018.03.015
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287