Adipose tissue plays an essential role in the regulation of many metabolic processes. Excess caloric intake and decreased energy expenditure cause adipocyte hypertrophy and hyperplasia, leading to inflammation of the adipose tissue, which contributes to obesity. Recent data link the Receptor for Advanced Glycation End-products (RAGE) to high fat diet (HFD)-induced obesity and subsequent metabolic dysfunction, but its function is incompletely understood. On HFD, the concentration of RAGE ligands, such as carboxy methyl lysine (CML) - advanced glycation end-products (AGE) epitopes, S100 calcium binding protein B (S100b), and high mobility group box 1 (HMGB1) increases, activating RAGE and resulting in inflammation. However, deletion of RAGE protected against the HFD-induced obesity and resulted in increased overall energy expenditure. In this study, we tested the hypothesis that the protective mechanism of RAGE deletion is due, in part, to browning which involves inducing brown adipose tissue (BAT)-like properties in white adipose tissue (WAT). The expression of uncoupling protein 1 (UCP1), which is usually only expressed in BAT, is increased in the WAT of RAGE knockout (RKO) mice. This effect was reproduced in vitro, by silencing the Ager gene in the adipocyte cell line C3H10T1/2. We propose that RAGE affects adipocyte phenotype by downregulating the expression of browning genes such as UCP1, and therefore is a key determinant of energy expenditure and adiposity. Thus, RAGE antagonism may promote BAT phenotype and function in WAT, reducing adiposity, which may have potential therapeutic implications for treating obesity. / 2017-03-31T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/14372 |
| Date | 22 January 2016 |
| Creators | Shim, Cynthia |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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