褐色脂肪组织分化及其调节机制研究进展

Brown Adipose Tissue Differentiation and Control Mechanism

人类和其他哺乳动物主要有两种脂肪组织:白色脂肪组织(又分为内脏和皮下两大类)和褐色脂肪组织;相对于内脏白色脂肪组织,皮下白色脂肪组织和褐色脂肪组织有利于改善糖代谢和能量消耗。人体内出现两种褐色脂肪组织的分化途径。BMP7 (bone morphogenetic proteins 7)是转化生长因子-β超家族成员(transforming growth,TGF-β)的多功能分泌型信号分子,在胚胎发生、个体形成、非对称器官的形成、胚胎的发育和损伤组织的修复中起关键作用。最近发现BMP7能促进褐色脂肪细胞的分化,可能是由于BMP7诱导PRDM16及PGC-1α等的基因表达,进一步增加了UCP1等基因的表达,最终诱导褐色脂肪细胞中线粒体的生物生成和随后的细胞分化。这些研究显示通过激活 BMP7和PRDM16 来增加褐色脂肪组织在治疗肥胖及相关疾病方面具有很大潜力。最近采用监测癌症及癌症转移的氟化脱氧葡萄糖–正电子发射计算机断层显像技术与(或)X-射线断层显像技术(18F-FDG-PET/CT)扫描技术并结合定位组织取样进行分子鉴定发现在成年人体内的确存在有功能活性的褐色脂肪组织,人们将其作为一个寻找治疗肥胖症新方法的重要靶标。

Humans and other mammals have two main adipose tissue depots: white adipose tissue (include visceral- and subcutaneous- white adipose tissue), and brown adipose tissue, each of which possesses unique cell-autonomous properties. In contrast to visceral adipose tissue, which can induce detrimental metabolic ef-fects, subcutaneous white adipose tissue and brown adipose tissue have the potential to benefit metabolism by improving glucose homeostasis and increasing energy consumption. BMP7 (bone morphogenetic proteins7) is one of members of the transforming growth factor-β (TGF-β) superfamily and control multiple key steps of embryonic development and differentiation. In recent studies, people found that BMP7-induced UCP1 ex-pression was markedly diminished in brown preadipocytes deficient in both PRDM16 and PGC (PGC-1α and PGC-1β), it ultimately induces BAT mitochondrial cells in the biological production and cell differentiation. There are two ways in development of brown adipose tissue. These researches indicate the potential to treat obesity and related diseases through activating BMP7 and PRDM16 to produce brown adipose tissue. Re-cently, using 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomographic and computed tomographic (PET-CT) scans showed that adults retain metabolically active BAT depots that can be induced in response to cold and sympathetic nervous system activation. These findings high light BAT as a potenial relevant tar get for pharmacological and gene expression manipulation to combat human obesity. We reviewed the recent re-search progresses of BAT in human and its potential functional significance.