Molecular control of brite adipogenesis: Identification of novel cell surface markers, transcriptional regulators and functional components

棕色（白色中的棕色）脂肪细胞是在啮齿动物和/或人类的白色脂肪组织（WAT）中发现的棕色脂肪细胞样细胞。与棕色脂肪细胞类似，棕色脂肪细胞中的线粒体解偶联蛋白1（UCP 1）在激活时可以直接耗散化学能作为热量，这一过程称为非颤抖性产热。在小鼠中，WAT中brite脂肪细胞的募集、维持和活化导致有益的代谢效应，例如抵抗饮食诱导的肥胖和改善的葡萄糖耐量。由于brite脂肪细胞代表了代谢性疾病的一个新的假定治疗靶点，本提案旨在从分子、发育和功能水平阐明brite脂肪细胞生物学的关键方面。基于原代培养的brite脂肪细胞的转录组数据，我们从5个具有不同brite脂肪形成倾向的近交系小鼠品系中选择了编码前体或brite脂肪细胞的细胞表面标志物、brite脂肪形成的转录调节因子和brite线粒体产热机制的功能组分的候选基因。我们将研究这些候选基因在原代细胞培养和体内脂肪细胞中的作用。

Brite (brown-in-white) adipocytes are brown adipocyte-like cells found in white adipose tissue (WAT) of rodents and/or humans. Similar to brown adipocytes, mitochondrial uncoupling protein 1 (UCP1) in brite adipocytes can directly dissipate chemical energy as heat upon activation, a process known as nonshivering thermogenesis. In mice the recruitment, maintenance and activation of brite adipocytes in WAT results in beneficial metabolic effects, such as resistance to diet-induced obesity and improved glucose tolerance. As brite adipocytes represent a new putative therapeutic target for metabolic diseases, this proposal aims to elucidate crucial aspects of brite adipocyte biology on the molecular, developmental and functional level. Based on transcriptome data of primary cultured brite adipocytes obtained from five inbred mouse strains with different propensity for brite adipogenesis we selected candidate genes encoding for cell surface markers of precursors or brite adipocytes, transcriptional regulators of brite adipogenesis and functional components of the thermogenic machinery in brite mitochondria. We will investigate the role of these candidate genes for brite adipocytes in primary cell culture as well as in vivo.