| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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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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