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Publication : A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism.

First Author  Seldin MM Year  2018
Journal  Cell Metab Volume  27
Issue  5 Pages  1138-1155.e6
PubMed ID  29719227 Mgi Jnum  J:262202
Mgi Id  MGI:6159436 Doi  10.1016/j.cmet.2018.03.015
Citation  Seldin MM, et al. (2018) A Strategy for Discovery of Endocrine Interactions with Application to Whole-Body Metabolism. Cell Metab 27(5):1138-1155.e6
abstractText  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.
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