FP30-4 Tissue Distribution and Potential Signaling Pathway of Adropin in Mice

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP30-Central Regulation of Appetite & Feeding
Basic
Monday, June 17, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 11:00 AM
Room 304 (Moscone Center)

Poster Board MON-653
Yudong Wang*1, Chi-Ming Wong1, Dewei Ye1, Aimin Xu2 and Karen SL Lam2
1The University of Hong Kong, Hong Kong, Hong Kong, 2University of Hong Kong, Hong Kong, Hong Kong
Adropin, encoded by the energy homeostasis associated (Enho) gene, is a peptide involved in the regulation of energy homeostasis and lipid metabolism as first identified in 2008 (1). Transgenic adropin overexpression or administration of synthetic adropin has been found to improve glucose homeostasis and attenuate hepatic steatosis in diet-induced obesity (1). On the contrary, adropin deficiency has been reported to be associated with increased adiposity and insulin resistance (2). However, its detailed pathophysiological functions and the underlying molecular mechanisms are still unclear. In the current study, we explored the tissue distribution of adropin in mice using Western blotting and found that adropin was preferentially expressed in the brain, especially in the brain stem, cerebellum, thalamus and hypothalamus. Meanwhile, analysis of the adropin subcellular localization through Phobius Predictive Program and Western blotting revealed adropin to be a membrane-bound protein but not a secreted protein. Furthermore, we performed the yeast two-hybrid screening and co-immunoprecipitation assays and identified the neural recognition molecule NB3, a membrane-tethered non-canonical Notch1 ligand (3), as a potential binding partner for adropin. The phenotyping studies of adropin knockout (AdrKO) mice showed that AdrKO mice exhibited decreased locomotor activity and impaired glucose tolerance coupled with decreased insulin sensitivity, compared to their wild type littermates. Taken together, our present data suggest that adropin is a brain-specific membrane-bound protein which interacts with the brain-specific Notch1 ligand NB3. It regulates energy homeostasis and glucose metabolism at least in part through its effect on physical activity, and hence body weight. The detailed molecular mechanism of the adropin/NB3/Notch1 signaling pathway warrants further investigation.

(1) Kumar KG et al., Cell Metab 2008; 8:468(2) Kumar KG et al., Obesity 2012; 20:1394(3) Guruharsha KG et al., Nat Rev Genet 2012; 13:654

Nothing to Disclose: YW, CMW, DY, AX, KSL

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Acknowledgment: This study was supported by the Collaborative Research Fund (Grant No.HKU3/09C) of the Hong Kong Research Grant Council.