Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors

Journal of Biological Chemistry

Volumn 288, Issue 45, 2013, Pages 32475-32489

  Simon, Becky R ^a   Parlee, Sebastian D ^b   Learman, Brian S ^b   Mori, Hiroyuki ^b   Scheller, Erica L ^b   Cawthorn, William P ^b,c   Ning, Xiaomin ^b   Gallagher, Katherine ^a   Tyrberg, Björn ^d,f   Assadi Porter, Fariba M ^e   Evans, Charles R ^b   MacDougald, Ormond A ^a,b  

^a UNIVERSITY OF MICHIGAN   (United States)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^c ELI LILLY AND COMPANY   (United States)

^d MEDIMMUNE   (United States)

^e UNIVERSITY OF WISCONSIN MADISON   (United States)

^f BURNHAM INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADIPOCYTE DIFFERENTIATION; ARTIFICIAL SWEETENERS; CAMP-RESPONSE ELEMENTS; CCAAT/ENHANCER-BINDING PROTEINS; G PROTEIN COUPLED RECEPTORS; HORMONE-SENSITIVE LIPASE; MESENCHYMAL STEM CELL; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR;

CELL CULTURE; DRUG PRODUCTS; ENZYMES; FOOD ADDITIVES; METABOLISM; MOLECULAR WEIGHT; PHOSPHORYLATION; PHYSIOLOGY; PROTEINS; SUGARS; TISSUE;

SUGAR SUBSTITUTES;

ACESULFAME; CCAAT ENHANCER BINDING PROTEIN ALPHA; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; DEXAMETHASONE; G PROTEIN COUPLED RECEPTOR; HORMONE SENSITIVE LIPASE; INSULIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SACCHARIN; SWEETENING AGENT; T1R2 PROTEIN; T1R3 PROTEIN; TRANSCRIPTION FACTOR FKHR; UNCLASSIFIED DRUG;

ADIPOGENESIS; ANIMAL CELL; ARTICLE; CELL DIFFERENTIATION; CELL STRAIN 3T3; CONTROLLED STUDY; GENE EXPRESSION; HUMAN; HUMAN CELL; LIPOLYSIS; MESENCHYMAL STEM CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROADIPOCYTE; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION;

ACESULFAME K; ADIPOGENESIS; AKT; G PROTEIN-COUPLED RECEPTORS (GPCR); LIPOLYSIS; METABOLISM; SACCHARIN; T1R2; T1R3;

3T3-L1 CELLS; ADIPOCYTES; ADIPOGENESIS; ADJUVANTS, IMMUNOLOGIC; ANIMALS; CCAAT-ENHANCER-BINDING PROTEIN-ALPHA; CELL DIFFERENTIATION; COLFORSIN; CYCLIC AMP; FEMALE; FORKHEAD TRANSCRIPTION FACTORS; HUMANS; LIPOLYSIS; MALE; MICE; MIDDLE AGED; PHOSPHATIDYLINOSITOL 3-KINASES; PHOSPHORYLATION; PPAR GAMMA; PROTO-ONCOGENE PROTEINS C-AKT; RECEPTORS, G-PROTEIN-COUPLED; SACCHARIN; STEM CELLS; STEROL ESTERASE; SWEETENING AGENTS;

EID: 84887490753     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M113.514034     Document Type: Article

References (68)

1. Rosen, E. D., and MacDougald, O. A. (2006) Adipocyte differentiation from the inside out. Nat. Rev. Mol. Cell Biol. 7, 885-896
2. Hong, Y. H., Nishimura, Y., Hishikawa, D., Tsuzuki, H., Miyahara, H., Gotoh, C., Choi, K. C., Feng, D. D., Chen, C., Lee, H. G., Katoh, K., Roh, S. G., and Sasaki, S. (2005) Acetate and propionate short chain fatty acids stimulate adipogenesis via GPCR43. Endocrinology 146, 5092-5099
3. Gotoh, C., Hong, Y. H., Iga, T., Hishikawa, D., Suzuki, Y., Song, S. H., Choi, K. C., Adachi, T., Hirasawa, A., Tsujimoto, G., Sasaki, S., and Roh, S. G. (2007) The regulation of adipogenesis through GPR120. Biochem. Biophys. Res. Commun. 354, 591-597
4. Saltiel, A. R., and Kahn, C. R. (2001) Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414, 799-806
5. Liu, C., Wu, J., Zhu, J., Kuei, C., Yu, J., Shelton, J., Sutton, S. W., Li, X., Yun, S. J., Mirzadegan, T., Mazur, C., Kamme, F., and Lovenberg, T. W. (2009) Lactate inhibits lipolysis in fat cells through activation of an orphan Gprotein- coupled receptor, GPR81. J. Biol. Chem. 284, 2811-2822
6. Taggart, A. K., Kero, J., Gan, X., Cai, T. Q., Cheng, K., Ippolito, M., Ren, N., Kaplan, R., Wu, K., Wu, T. J., Jin, L., Liaw, C., Chen, R., Richman, J., Connolly, D., Offermanns, S., Wright, S. D., and Waters, M. G. (2005) D-β-Hydroxybutyrate inhibits adipocyte lipolysis via the nicotinic acid receptor PUMA-G. J. Biol. Chem. 280, 26649-26652
7. Ren, N., Kaplan, R., Hernandez, M., Cheng, K., Jin, L., Taggart, A. K., Zhu, A. Y., Gan, X., Wright, S. D., and Cai, T. Q. (2009) Phenolic acids suppress adipocyte lipolysis via activation of the nicotinic acid receptor GPR109A (HM74a/PUMA-G). J. Lipid Res. 50, 908-914
8. Ahmed, K., Tunaru, S., and Offermanns, S. (2009) GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors. Trends Pharmacol. Sci. 30, 557-562
9. Duncan, R. E., Sarkadi-Nagy, E., Jaworski, K., Ahmadian, M., and Sul, H. S. (2008) Identification and functional characterization of adipose-specific phospholipase A2 (AdPLA). J. Biol. Chem. 283, 25428-25436
10. Nelson, G., Hoon, M. A., Chandrashekar, J., Zhang, Y., Ryba, N. J., and Zuker, C. S. (2001) Mammalian sweet taste receptors. Cell 106, 381-390
11. Zhao, G. Q., Zhang, Y., Hoon, M. A., Chandrashekar, J., Erlenbach, I., Ryba, N. J., and Zuker, C. S. (2003) The receptors for mammalian sweet and umami taste. Cell 115, 255-266
12. Xu, H., Staszewski, L., Tang, H., Adler, E., Zoller, M., and Li, X. (2004) Different functional roles of T1R subunits in the heteromeric taste receptors. Proc. Natl. Acad. Sci. U.S.A. 101, 14258-14263
13. Nie, Y., Vigues, S., Hobbs, J. R., Conn, G. L., and Munger, S. D. (2005) Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli. Curr. Biol. 15, 1948-1952
14. Elliott, R. A., Kapoor, S., and Tincello, D. G. (2011) Expression and distribution of the sweet taste receptor isoforms T1R2 and T1R3 in human and rat bladders. J. Urol. 186, 2455-2462
15. Ren, X., Zhou, L., Terwilliger, R., Newton, S. S., and de Araujo, I. E. (2009) Sweet taste signaling functions as a hypothalamic glucose sensor. Front. Integr. Neurosci. 3, 12
16. Dyer, J., Salmon, K. S., Zibrik, L., and Shirazi-Beechey, S. P. (2005) Expression of sweet taste receptors of the T1R family in the intestinal tract and enteroendocrine cells. Biochem. Soc. Trans. 33, 302-305
17. Nakagawa, Y., Nagasawa, M., Yamada, S., Hara, A., Mogami, H., Nikolaev, V. O., Lohse, M. J., Shigemura, N., Ninomiya, Y., and Kojima, I. (2009) Sweet taste receptor expressed in pancreatic β-cells activates the calcium and cyclic AMP signaling systems and stimulates insulin secretion. PLoS One 4, e5106
18. Jang, H. J., Kokrashvili, Z., Theodorakis, M. J., Carlson, O. D., Kim, B. J., Zhou, J., Kim, H. H., Xu, X., Chan, S. L., Juhaszova, M., Bernier, M., Mosinger, B., Margolskee, R. F., and Egan, J. M. (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc. Natl. Acad. Sci. U.S.A. 104, 15069-15074
19. Mace, O. J., Affleck, J., Patel, N., and Kellett, G. L. (2007) Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2. J. Physiol. 582, 379-392
20. Kyriazis, G. A., Soundarapandian, M. M., and Tyrberg, B. (2012) Sweet taste receptor signaling in β cells mediates fructose-induced potentiation of glucose-stimulated insulin secretion. Proc. Natl. Acad. Sci. U.S.A. 109, E524-E532
21. Jiang, P., Cui, M., Zhao, B., Liu, Z., Snyder, L. A., Benard, L. M., Osman, R., Margolskee, R. F., and Max, M. (2005) Lactisole interacts with the transmembrane domains of human T1R3 to inhibit sweet taste. J. Biol. Chem. 280, 15238-15246
22. Masuda, K., Koizumi, A., Nakajima, K., Tanaka, T., Abe, K., Misaka, T., and Ishiguro, M. (2012) Characterization of the modes of binding between human sweet taste receptor and low-molecular-weight sweet compounds. PLoS One 7, e35380
23. Treesukosol, Y., Blonde, G. D., and Spector, A. C. (2009) T1R2 and T1R3 subunits are individually unnecessary for normal affective licking responses to Polycose: implications for saccharide taste receptors in mice. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, R855-R865
24. Zukerman, S., Glendinning, J. I., Margolskee, R. F., and Sclafani, A. (2009) T1R3 taste receptor is critical for sucrose but not Polycose taste. Am. J. Physiol. Regul. Integr. Comp. Physiol. 296, R866-R876
25. Nie, Y., Hobbs, J. R., Vigues, S., Olson, W. J., Conn, G. L., and Munger, S. D. (2006) Expression and purification of functional ligand-binding domains of T1R3 taste receptors. Chem. Senses 31, 505-513
26. Maîtrepierre, E., Sigoillot, M., Le Pessot, L., and Briand, L. (2012) Recombinant expression, in vitro refolding, and biophysical characterization of the N-terminal domain of T1R3 taste receptor. Protein Expr. Purif. 83, 75-83
27. Hemati, N., Ross, S. E., Erickson, R. L., Groblewski, G. E., and MacDougald, O. A. (1997) Signaling pathways through which insulin regulates CCAAT/enhancer binding protein a (C/EBPα) phosphorylation and gene expression in 3T3-L1 adipocytes: correlation with GLUT4 gene expression. J. Biol. Chem. 272, 25913-25919
28. Cawthorn, W. P., Bree, A. J., Yao, Y., Du, B., Hemati, N., Martinez-Santibañez, G., and MacDougald, O. A. (2012) Wnt6, Wnt10a and Wnt10b inhibit adipogenesis and stimulate osteoblastogenesis through a β-catenin-dependent mechanism. Bone 50, 477-489
29. Rim, J. S., Mynatt, R. L., and Gawronska-Kozak, B. (2005) Mesenchymal stem cells from the outer ear: a novel adult stem cell model system for the study of adipogenesis. FASEB J. 19, 1205-1207
30. Mori, H., Prestwich, T. C., Reid, M. A., Longo, K. A., Gerin, I., Cawthorn, W. P., Susulic, V. S., Krishnan, V., Greenfield, A., and Macdougald, O. A. (2012) Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition. J. Clin. Investig. 122, 2405-2416
31. Lorenz, M. A., Burant, C. F., and Kennedy, R. T. (2011) Reducing time and increasing sensitivity in sample preparation for adherent mammalian cell metabolomics. Anal. Chem. 83, 3406-3414
32. Venkitakrishnan, R. P., Benard, O., Max, M., Markley, J. L., and Assadi- Porter, F. M. (2012) Use of NMR saturation transfer difference spectroscopy to study ligand binding to membrane proteins. Methods Mol. Biol. 914, 47-63
33. Sweatman, T. W., and Renwick, A. G. (1979) Saccharin metabolism and tumorigenicity. Science 205, 1019-1020
34. Renwick, A. G. (1986) The metabolism of intense sweeteners. Xenobiotica 16, 1057-1071
35. Liu, D., and Liman, E. R. (2003) Intracellular Ca2+ and the phospholipid PIP2 regulate the taste transduction ion channel TRPM5. Proc. Natl. Acad. Sci. U.S.A. 100, 15160-15165
36. Nakae, J., Kitamura, T., Kitamura, Y., Biggs, W. H., 3rd, Arden, K. C., and Accili, D. (2003) The forkhead transcription factor Foxo1 regulates adipocyte differentiation. Dev. Cell 4, 119-129
37. Menghini, R., Marchetti, V., Cardellini, M., Hribal, M. L., Mauriello, A., Lauro, D., Sbraccia, P., Lauro, R., and Federici, M. (2005) Phosphorylation of GATA2 by Akt increases adipose tissue differentiation and reduces adipose tissue-related inflammation: a novel pathway linking obesity to atherosclerosis. Circulation 111, 1946-1953
38. Kim, S. P., Ha, J. M., Yun, S. J., Kim, E. K., Chung, S. W., Hong, K. W., Kim, C. D., and Bae, S. S. (2010) Transcriptional activation of peroxisome proliferator- activated receptor-gamma requires activation of both protein kinase A and Akt during adipocyte differentiation. Biochem. Biophys. Res. Commun. 399, 55-59
39. Magun, R., Burgering, B. M., Coffer, P. J., Pardasani, D., Lin, Y., Chabot, J., and Sorisky, A. (1996) Expression of a constitutively activated form of protein kinase B (c-Akt) in 3T3-L1 preadipose cells causes spontaneous differentiation. Endocrinology 137, 3590-3593
40. Klemm, D. J., Leitner, J. W., Watson, P., Nesterova, A., Reusch, J. E., Goalstone, M. L., and Draznin, B. (2001) Insulin-induced adipocyte differentiation. Activation of CREB rescues adipogenesis from the arrest caused by inhibition of prenylation. J. Biol. Chem. 276, 28430-28435
41. Cypess, A. M., Zhang, H., Schulz, T. J., Huang, T. L., Espinoza, D. O., Kristiansen, K., Unterman, T. G., and Tseng, Y. H. (2011) Insulin/IGF-I regulation of necdin and brown adipocyte differentiation via CREB- and FoxO1-associated pathways. Endocrinology 152, 3680-3689
42. Damak, S., Rong, M., Yasumatsu, K., Kokrashvili, Z., Varadarajan, V., Zou, S., Jiang, P., Ninomiya, Y., and Margolskee, R. F. (2003) Detection of sweet and umami taste in the absence of taste receptor T1r3. Science 301, 850-853
43. Geraedts, M. C., Takahashi, T., Vigues, S., Markwardt, M. L., Nkobena, A., Cockerham, R. E., Hajnal, A., Dotson, C. D., Rizzo, M. A., and Munger, S. D. (2012) Transformation of postingestive glucose responses after deletion of sweet taste receptor subunits or gastric bypass surgery. Am. J. Physiol. Endocrinol. Metab. 303, E464-E474
44. Dergance, J. M., Mouton, C. P., Lichtenstein, M. J., and Hazuda, H. P. (2005) Potential mediators of ethnic differences in physical activity in older Mexican Americans and European Americans: results from the San Antonio Longitudinal Study of Aging. J. Am. Geriatr. Soc. 53, 1240-1247
45. Rodin, J. (1990) Comparative effects of fructose, aspartame, glucose, and water preloads on calorie and macronutrient intake. Am. J. Clin. Nutr. 51, 428-435
46. Porikos, K. P., and Koopmans, H. S. (1988) The effect of non-nutritive sweeteners on body weight in rats. Appetite 11, Suppl. 1, 12-15
47. Blackburn, G. L., Kanders, B. S., Lavin, P. T., Keller, S. D., and Whatley, J. (1997) The effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight. Am. J. Clin. Nutr. 65, 409-418
48. Swithers, S. E., Martin, A. A., and Davidson, T. L. (2010) High-intensity sweeteners and energy balance. Physiol. Behav. 100, 55-62
49. Swithers, S. E., and Davidson, T. L. (2008) A role for sweet taste: calorie predictive relations in energy regulation by rats. Behav. Neurosci. 122, 161-173
50. Anderson, G. H., Foreyt, J., Sigman-Grant, M., and Allison, D. B. (2012) The use of low-calorie sweeteners by adults: impact on weight management. J. Nutr. 142, 1163S-1169S
51. Sweatman, T. W., Renwick, A. G., and Burgess, C. D. (1981) The pharmacokinetics of saccharin in man. Xenobiotica 11, 531-540
52. Colburn, W. A., Bekersky, I., and Blumenthal, H. P. (1981) Dietary saccharin kinetics. Clin. Pharmacol. Ther. 30, 558-563
53. Colburn, W. A., Bekersky, I., and Blumenthal, H. P. (1981) A preliminary report on the pharmacokinetics of saccharin in man: single oral dose administration. J. Clin. Pharmacol. 21, 147-151
54. Pantarotto, C., Salmona, M., and Garattini, S. (1981) Plasma kinetics and urinary elimination of saccharin in man. Toxicol. Lett. 9, 367-371
55. Masubuchi, Y., Nakagawa, Y., Ma, J., Sasaki, T., Kitamura, T., Yamamoto, Y., Kurose, H., Kojima, I., and Shibata, H. (2013) A novel regulatory function of sweet taste-sensing receptor in adipogenic differentiation of 3T3-L1 cells. PLoS One 8, e54500
56. Striem, B. J., Naim, M., Zehavi, U., and Ronen, T. (1990) Saccharin induces changes in adenylate cyclase activity in liver and muscle membranes in rats. Life Sci. 46, 803-810
57. Dib, K., Oget, I., Wrisez, F., El Jamali, A., Aguie-Aguie, G., Correze, C., and Lambert, B. (1996) Effects of sodium saccharin diet on fat-cell lipolysis: evidence for increased function of the adenylyl cyclase catalyst. Int. J. Obes. Relat. Metab. Disord. 20, 15-20
58. Dib, K., Wrisez, F., el Jamali, A., Lambert, B., and Correze, C. (1997) Sodium saccharin inhibits adenylyl cyclase activity in non-taste cells. Cell. Signal. 9, 431-438
59. Andrabi, S., Gjoerup, O. V., Kean, J. A., Roberts, T. M., and Schaffhausen, B. (2007) Protein phosphatase 2A regulates life and death decisions via Akt in a context-dependent manner. Proc. Natl. Acad. Sci. U.S.A. 104, 19011-19016
60. Huang, C. Y., and Tan, T. H. (2012) DUSPs, to MAP kinases and beyond. Cell Biosci. 2, 24
61. Bartoshuk, L. M. (1979) Bitter taste of saccharin related to the genetic ability to taste the bitter substance 6-n-propylthiouracil. Science 205, 934-935
62. Kuhn, C., Bufe, B., Winnig, M., Hofmann, T., Frank, O., Behrens, M., Lewtschenko, T., Slack, J. P., Ward, C. D., and Meyerhof, W. (2004) Bitter taste receptors for saccharin and acesulfame K. J. Neurosci. 24, 10260-10265
63. Lund, T. C., Kobs, A. J., Kramer, A., Nyquist, M., Kuroki, M. T., Osborn, J., Lidke, D. S., Low-Nam, S. T., Blazar, B. R., and Tolar, J. (2013) Bone marrow stromal and vascular smooth muscle cells have chemosensory capacity via bitter taste receptor expression. PLoS One 8, e58945
64. Meyerhof, W., Batram, C., Kuhn, C., Brockhoff, A., Chudoba, E., Bufe, B., Appendino, G., and Behrens, M. (2010) The molecular receptive ranges of human TAS2R bitter taste receptors. Chem. Senses 35, 157-170
65. Brockhoff, A., Behrens, M., Massarotti, A., Appendino, G., and Meyerhof, W. (2007) Broad tuning of the human bitter taste receptor hTAS2R46 to various sesquiterpene lactones, clerodane and labdane diterpenoids, strychnine, and denatonium. J. Agric. Food Chem. 55, 6236-6243
66. Slack, J. P., Brockhoff, A., Batram, C., Menzel, S., Sonnabend, C., Born, S., Galindo, M. M., Kohl, S., Thalmann, S., Ostopovici-Halip, L., Simons, C. T., Ungureanu, I., Duineveld, K., Bologa, C. G., Behrens, M., Furrer, S., Oprea, T. I., and Meyerhof, W. (2010) Modulation of bitter taste perception by a small molecule hTAS2R antagonist. Curr. Biol. 20, 1104-1109
67. Markus, H. B., and Ball, E. G. (1969) Inhibition of lipolytic processes in rat adipose tissue by antimalaria drugs. Biochim. Biophys. Acta 187, 486-491
68. Wauson, E. M., Zaganjor, E., Lee, A. Y., Guerra, M. L., Ghosh, A. B., Bookout, A. L., Chambers, C. P., Jivan, A., McGlynn, K., Hutchison, M. R., Deberardinis, R. J., and Cobb, M. H. (2012) The G protein-coupled taste receptor T1R1/T1R3 regulates mTORC1 and autophagy. Mol. Cell 47, 851-862