Role of Sweet Taste Receptors in Adipocyte Differentiation and Metabolism

描述（由申请人提供）：在我们对脂肪形成程序的理解以及正向和负向调节前脂肪细胞分化的信号通路方面取得了巨大进展。然而，目前还不清楚脂肪组织如何感知“营养过剩”状态以刺激脂肪生成。基于我们的初步数据，我们提出了这样的假设，即甜味受体T1R2和T1R3的激活通过刺激前脂肪细胞的分化和减少脂肪细胞的脂解而有助于脂肪组织的扩张。为了验证这些假设，我们提出了多种体外和体内方法来研究感觉受体激活增加脂肪细胞数量和大小的机制。本申请的具体目的是1）研究甜味和其他感觉受体刺激脂肪形成的机制，和2）研究甜味受体对脂肪细胞脂解的抑制和对代谢的其他方面的调节。这些特定目标的成功完成将提高我们对营养信号如何转导以调节脂肪细胞分化和代谢的理解。了解这些过程可能会提供深入了解脂肪细胞增生和肥胖肥大的原因，并阐明代谢综合征的各个方面，包括II型糖尿病。

DESCRIPTION (provided by applicant): 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.