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Predicted secreted protein analysis reveals synaptogenic function of Clstn3 during WAT browning and bat activation in mice

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Acta Pharmacologica Sinica 2019年第8期40卷 999-1009页

作者： Shu-qin Chen Qiang Niu Li-ping Ju Miriayi Alimujiang Han Yan Ning-ning Bai Jun Xu Qi-chen Fang Jun-feng Han Ying Yang Wei-ping Jia Shanghai Key Laboratory of Diabetes Shanghai Institute for DiabetesShanghai Clinical Medical Centre of DiabetesShanghai Key Clinical Centre of Metabolic DiseasesDepartment of Endocrinology and MetabolismShanghai Jiao Tong University Affiliated Sixth People’s Hospital National Engineering Research Center of Die and Mold CAD Shanghai Jiao Tong University Department of Geriatrics Shanghai Jiao Tong University Affiliated Sixth People’s Hospital

Promoting white adipose tissue(WAT)browning and enhancing brown adipose tissue(bat)activity are attractive therapeutic strategies for obesity and its metabolic *** sympathetic innervation in WAT and bat represents a promising therapeutic ***,there are few reports on extracellular microenvironment remodeling,especially changes in nerve terminal *** the key molecules mediating the neuro-adipose synaptic junctions is a key *** this study,we used bioinformatics methods to identify the differentially expressed predicted secreted genes(DEPSGs)during WAT browning and bat *** DEPSGs largely reflect changes of cytokines,extracellular matrix remodeling,vascularization,and adipocyteneuronal *** then performed functional enrichment and cellular distribution specificity *** upregulated and downregulated DEPDGs during WAT browning displayed a distinctive biological pattern and cellular *** listed a cluster of adipocyte-enriched DEPSGs,which might participate in the cross-talk between mature adipocytes and other cells;then identified a synaptogenic adhesion molecule,Clstn3,as the top gene expressed enriched in both mature white and brown *** Q-PCR and immunohistochemistry,we found significantly increased Clstn3 expression level during WAT browning and bat activation in mice subjected to cold exposure(4℃).We further demonstrated that treatment with isoproterenol significantly increased Clstn3 and UCP1 expression in differentiated white and beige adipocytes in *** conclusion,our study demonstrates that the secretion pattern was somewhat different between WAT browning and bat *** reveal that Clstn3 may be a key gene mediating the neuro-adipose junction formation or remodeling in WAT browning and bat activation process.

关键词： WAT browning bat activation Calsyntenin-3 neuro-adipose synapse isoproterenol obesity

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