2016 Fiscal Year Final Research Report
Role of non-canonical T1R3 homomeric sweet receptor in adipogenesis and glucose transport
| Project/Area Number |
26461325
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Gunma University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 甘味受容体 / 脂肪細胞 / 微小管 / Rho / サイトカイン |
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| Outline of Final Research Achievements |
3T3-L1 cells express a functional sweet taste receptor as a T1R3 homomer that negatively regulates adipogenesis by a Gαs-mediated but cAMP-independent mechanism. In this study, we show that stimulation of this receptor induced microtubules disassembly in 3T3-L1 preadipocytes, which was attenuated by overexpression of the dominant-negative mutant of Gαs (Gαs-G226A) and mimicked by overexpression of the constitutively active mutant of Gαs (Gαs-Q227L). Sweetener also activated RhoA and Rho-associated kinase (ROCK), which was attenuated with by knockdown of GEF-H1, a microtubule-localized RhoGEF. Overexpression of the dominant-negative mutant of RhoA (RhoA-T19N) blocked sweetener-induced dephosphorylation of Akt and repression of PPARγ and C/EBPα in the early phase of adipogenic differentiation. Thus, the T1R3 homomeric sweet taste receptor negatively regulates adipogenesis through Gαs-mediated microtubule disassembly and consequent activation of the Rho/ROCK pathway.
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| Free Research Field |
細胞生物学，代謝学
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