Regulation of Adipocyte Differentiation and Metabolism by Artificial Sweeteners and Sweet Taste Receptors.
dc.contributor.author | Simon, Becky R. | en_US |
dc.date.accessioned | 2013-09-24T16:01:01Z | |
dc.date.available | NO_RESTRICTION | en_US |
dc.date.available | 2013-09-24T16:01:01Z | |
dc.date.issued | 2013 | en_US |
dc.date.submitted | en_US | |
dc.identifier.uri | https://hdl.handle.net/2027.42/99775 | |
dc.description.abstract | To maintain energetic homeostasis, adipose tissue must be uniquely sensitive to nutritional status. One mechanism for nutrient sensing in metabolic systems is through sweet taste receptors, which are intrinsically sensitive to carbohydrate. On the tongue, sweet taste is perceived by a heterodimer of the G protein-coupled receptors T1R2 and T1R3, which bind sugars to generate a ‘sweet’ taste response. These receptors also have extra-gustatory expression, and their ability to bind carbohydrate has spurred investigation into their role in nutrient sensing. Indeed, in enteroendocrine and beta cells, taste receptor activation stimulates GLP-1 and insulin secretion, respectively. However, a role for these receptors in adipose tissue has not been investigated. We have observed that T1R2 and T1R3 are also expressed in 3T3-L1 cells and mesenchymal stem cells. To assess effects of receptor activation on adipogenesis, we treated preadipocytes with artificial sweeteners saccharin and acesulfame potassium. We observed that both sweeteners robustly stimulated adipogenesis in mouse and human precursors. Saccharin treatment also stimulated phosphorylation of Akt and its downstream effectors, a likely mechanism for enhanced adipogenesis. However, we observed that neither T1R2 nor T1R3 expression was necessary for saccharin-stimulated adipogenesis. In mature adipocytes, artificial sweetener treatment also suppressed lipolysis. However, T1R2 and T1R3 were not required for this effect. These data suggest involvement of an additional ‘sweet’ receptor to mediate sweetener signaling. Concurrent with in vitro studies, we evaluated T1R2 and T1R3 KO mice for adipose tissue phenotypes. We hypothesized that these mice might have fewer adipocytes from failures in adipogenesis, or smaller adipocytes from unregulated lipolysis. We observed that while fat mass and adipocyte size is reduced in T1R2 and T1R3 KO animals, adipocyte number remains the same. This reduction in fat mass occurred without changes in food intake, energy expenditure, or glucose tolerance in T1R2 KO animals. Interestingly, bone marrow adipocyte number was decreased with T1R2 KO, and bone mass was increased in both genotypes. Taken together, these data suggest that sweet taste receptors may have important roles regulating bone mass and adiposity in vivo, but additional receptors are likely present to mediate the non-specific effects of artificial sweeteners. | en_US |
dc.language.iso | en_US | en_US |
dc.subject | Adipogenesis | en_US |
dc.subject | Nutrient Sensing | en_US |
dc.subject | Taste Receptors | en_US |
dc.title | Regulation of Adipocyte Differentiation and Metabolism by Artificial Sweeteners and Sweet Taste Receptors. | en_US |
dc.type | Thesis | en_US |
dc.description.thesisdegreename | PhD | en_US |
dc.description.thesisdegreediscipline | Cellular & Molecular Biology | en_US |
dc.description.thesisdegreegrantor | University of Michigan, Horace H. Rackham School of Graduate Studies | en_US |
dc.contributor.committeemember | MacDougald, Ormond A. | en_US |
dc.contributor.committeemember | Kennedy, Robert T. | en_US |
dc.contributor.committeemember | Lin, Jiandie | en_US |
dc.contributor.committeemember | Lumeng, Carey Nien-kai | en_US |
dc.contributor.committeemember | Pletcher, Scott | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/99775/1/simonbec_1.pdf | |
dc.owningcollname | Dissertations and Theses (Ph.D. and Master's) |
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