| First Author | Li Q | Year | 2018 |
| Journal | Mol Cell Biol | PubMed ID | 29358218 |
| Mgi Jnum | J:262883 | Mgi Id | MGI:6155986 |
| Doi | 10.1128/MCB.00562-17 | Citation | Li Q, et al. (2018) TCF7/TCF1 feedback controls osteocalcin signaling in brown adipocytes independent of canonical WNT/beta-catenin pathway. Mol Cell Biol |
| abstractText | Osteocalcin has recently been shown to regulate energy homeostasis through multiple pathways. Adipose tissue is a main organ of energy metabolism, and administration of recombinant osteocalcin in mice promoted energy consumption, thus counteracting obesity and glucose intolerance. The regulation of osteocalcin in islet beta cells has been well documented; however, it is unknown whether osteocalcin can also act on adipocytes, and if does, how it functions. Here, we provided evidence to demonstrate a specific role for osteocalcin in brown adipocyte thermogenesis. Importantly, expression of Gprc6a gene encoding a G protein-coupled receptor as osteocalcin receptor was activated by brown-fat-like differentiation. Moreover, Gprc6a expression could be further potentiated by osteocalcin. Meanwhile, overexpression and knockdown experiments validated its crucial role in osteocalcin-mediated thermogenic genes' activation. For the first time, we identified Tcf7 and Wnt3a as putative targets for osteocalcin signaling. TCF7 belongs to TCF/LEF1 family DNA binding factors crucial for canonical WNT/beta-catenin pathway; however, TCF7 modulates Gprc6a and Ucp1 promoter activation independent of beta-catenin. Further studies revealed that thermogenesis coactivator PRDM16 and histone demethylase LSD1 might be required for TCF7 activity. Hence, our study described a TCF7-dependent feedback control of osteocalcin-GPRC6A axis in brown adipocyte physiologies. |
