Role of Sweet Taste Receptors in Adipocyte Differentiation and Metabolism

描述(由申请者提供)：我们对脂肪形成的程序以及积极和消极调节前脂肪细胞分化的信号通路的理解已经取得了巨大的进展。然而，目前尚不清楚脂肪组织是如何感觉到“过度营养”状态来刺激脂肪生成的。基于我们的初步数据，我们提出以下假设：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促进脂肪组织的扩张。为了验证这些假设，我们提出了各种体外和体内方法来研究感官受体激活增加脂肪细胞的数量和大小的机制。这一应用的具体目的是1)研究甜味和其他感官受体刺激脂肪生成的机制；2)研究甜味受体抑制脂肪细胞脂肪分解和调节其他方面的代谢。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。了解这些过程可能有助于深入了解肥胖引起的脂肪细胞增殖和肥大的原因，并有助于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.