Artificial Sweeteners Stimulate Adipogenesis and Suppress Lipolysis Inependent of Sweet Taste Receptors
Simon, BR; Parlee, SD; Learman, BS; Mori, H; Scheller, EL; Cawthorn, WP; Ning, X; Gallagher, KA; Tyrberg, B; Assadi-Porter, FM; Evans, CR; Macdougald, OA
2013-01-01
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Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors.pdf
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Abstract
Gprotein-coupled receptors mediate responses to a myriad of ligands, some of which regulate adipocyte differentiation and metabolism. The sweet taste receptors T1R2 and T1R3 are G protein-coupled receptors that function as carbohydrate sensors in taste buds, gut, and pancreas. Here we report that sweet taste receptors T1R2 and T1R3 are expressed throughout adipogenesis and in adipose tissues. Treatment of mouse and human precursor cells with artificial sweeteners, saccharin and acesulfame potassium, enhanced adipogenesis. Saccharin treatment of 3T3-L1 cells and primary mesenchymal stem cells rapidly stimulated phosphorylation of Akt and downstream targets with functions in adipogenesis such as cAMP-response element- binding protein and FOXO1; however, increased expression of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α was not observed until relatively late in differentiation. Saccharin-stimulated Akt phosphorylation at Thr-308 occurred within 5 min, was phosphatidylinositol 3-kinase-dependent, and occurred in the presence of high concentrations of insulin and dexamethasone; phosphorylation of Ser-473 occurred more gradually. Surprisingly, neither saccharin-stimulated adipogenesis nor Thr-308 phosphorylation was dependent on expression of T1R2 and/or T1R3, although Ser-473 phosphorylation was impaired in T1R2/T1R3 double knock-out precursors. In mature adipocytes, artificial sweetener treatment suppressed lipolysis even in the presence of forskolin, and lipolytic responses were correlated with phosphorylation of hormone-sensitive lipase. Suppression of lipolysis by saccharin in adipocytes was also independent of T1R2 and T1R3. These results suggest that some artificial sweeteners have previously uncharacterized metabolic effects on adipocyte differentiation and metabolism and that effects of artificial sweeteners on adipose tissue biology may be largely independent of the classical sweet taste receptors, T1R2 and T1R3. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.Publisher
Elsevier
ISSN
0021-9258 1083-351X
Deep Blue DOI
Other DOIs
PMID
24068707
Subjects
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 Box Protein O1 Forkhead Transcription Factors Humans Lipolysis Male Mice Middle Aged PPAR gamma Phosphatidylinositol 3-Kinases Phosphorylation Proto-Oncogene Proteins c-akt Receptors, G-Protein-Coupled Saccharin Stem Cells Sterol Esterase Sweetening Agents
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