title: A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells.
abstract: BACKGROUND
  Sweet taste receptor is expressed not only in taste buds but also in nongustatory organs such as enteroendocrine cells and pancreatic beta-cells, and may play more extensive physiological roles in energy metabolism. Here we examined the expression and function of the sweet taste receptor in 3T3-L1 cells.
  
  
  RESULTS
  In undifferentiated preadipocytes, both T1R2 and T1R3 were expressed very weakly, whereas the expression of T1R3 but not T1R2 was markedly up-regulated upon induction of differentiation (by 83.0 and 3.8-fold, respectively at Day 6). The α subunits of Gs (Gαs) and G14 (Gα14) but not gustducin were expressed throughout the differentiation process. The addition of sucralose or saccharin during the first 48 hours of differentiation considerably reduced the expression of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer-binding protein α (C/EBPα at Day 2, the expression of aP2 at Day 4 and triglyceride accumulation at Day 6. These anti-adipogenic effects were attenuated by short hairpin RNA-mediated gene-silencing of T1R3. In addition, overexpression of the dominant-negative mutant of Gαs but not YM-254890, an inhibitor of Gα14, impeded the effects of sweeteners, suggesting a possible coupling of Gs with the putative sweet taste-sensing receptor. In agreement, sucralose and saccharin increased the cyclic AMP concentration in differentiating 3T3-L1 cells and also in HEK293 cells heterologously expressing T1R3. Furthermore, the anti-adipogenic effects of sweeteners were mimicked by Gs activation with cholera toxin but not by adenylate cyclase activation with forskolin, whereas small interfering RNA-mediated knockdown of Gαs had the opposite effects.
  
  
  CONCLUSIONS
  3T3-L1 cells express a functional sweet taste-sensing receptor presumably as a T1R3 homomer, which mediates the anti-adipogenic signal by a Gs-dependent but cAMP-independent mechanism.
authors: Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors: Yosuke
authors: Y
authors: Masubuchi
authors: Yuko
authors: Y
authors: Nakagawa
authors: Jinhui
authors: J
authors: Ma
authors: Tsutomu
authors: T
authors: Sasaki
authors: Tadahiro
authors: T
authors: Kitamura
authors: Yoritsuna
authors: Y
authors: Yamamoto
authors: Hitoshi
authors: H
authors: Kurose
authors: Itaru
authors: I
authors: Kojima
authors: Hiroshi
authors: H
authors: Shibata
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D013650:Taste Buds / Q000502:physiology*
chemical_list: D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D000242:Cyclic AMP; D019204:GTP-Binding Proteins