Tremendous progress has been made in our understanding of the program of adipogenesis, and the signaling pathways that positively and negatively regulate preadipocyte differentiation. However, it remains unclear how adipose tissues sense a state of "over-nutrition" to stimulate adipogenesis. Based on our preliminary data, we propose the hypotheses that activation of sweet taste receptors T1R2 and T1R3 contribute to expansion of adipose tissue by stimulating differentiation of preadipocytes, and decreasing lipolysis of adipocytes. To test these hypotheses, we propose a variety of in vitro and in vivo approaches to investigate the mechanisms through which sensory receptor activation increases the number and size of adipocytes.
The specific aims of this application are to 1) investigate mechanisms by which sweet taste and other sensory receptors stimulate adipogenesis and 2) to investigate the repression of adipocyte lipolysis and regulation of other aspects of metabolism by sweet taste receptors. Successful completion of these specific aims will improve our understanding of how nutrients signals are transduced to regulate adipocyte differentiation and metabolism. Understanding these processes may provide insights into the causes of adipocyte hyperplasia and hypertrophy with obesity, and shed light on aspects of the metabolic syndrome, including type II diabetes.
The proposed research will increase our understanding of how activation of sweet taste receptors by artificial sweeteners (e.g. saccharin) and naturally occurring metabolites regulates expansion of white fat through effects on both development and metabolism of fat cells. Understanding these processes may provide insights into the increase in adipocyte number and size that occurs with obesity, and also shed light on how obesity predisposes to metabolic complications such as type II diabetes.
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|Parlee, Sebastian D; Simon, Becky R; Scheller, Erica L et al. (2014) Administration of saccharin to neonatal mice influences body composition of adult males and reduces body weight of females. Endocrinology 155:1313-26|
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|Simon, Becky R; Learman, Brian S; Parlee, Sebastian D et al. (2014) Sweet taste receptor deficient mice have decreased adiposity and increased bone mass. PLoS One 9:e86454|
|Parlee, Sebastian D; Lentz, Stephen I; Mori, Hiroyuki et al. (2014) Quantifying size and number of adipocytes in adipose tissue. Methods Enzymol 537:93-122|
|Simon, Becky R; Parlee, Sebastian D; Learman, Brian S et al. (2013) Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors. J Biol Chem 288:32475-89|