Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts,USA.
Diabetes. 2012 Jul;61(7):1691-9. doi: 10.2337/db11-1753. Epub 2012 May 17.
Obesity and body fat distribution are important risk factors for the development of type 2 diabetes and metabolic syndrome. Evidence has accumulated that this risk is related to intrinsic differences in behavior of adipocytes in different fat depots. In the current study, we demonstrate that adipocyte precursor cells (APCs) isolated from visceral and subcutaneous white adipose depots of mice have distinct patterns of gene expression, differentiation potential, and response to environmental and genetic influences. APCs derived from subcutaneous fat differentiate well in the presence of classical induction cocktail, whereas those from visceral fat differentiate poorly but can be induced to differentiate by addition of bone morphogenetic protein (BMP)-2 or BMP-4. This difference correlates with major differences in gene expression signature between subcutaneous and visceral APCs. The number of APCs is higher in obesity-prone C57BL/6 mice than obesity-resistant 129 mice, and the number in both depots is increased by up to 270% by exposure of mice to high-fat diet. Thus, APCs from visceral and subcutaneous depots are dynamic populations, which have intrinsic differences in gene expression, differentiation properties, and responses to environmental/genetic factors. Regulation of these populations may provide a new target for the treatment and prevention of obesity and its metabolic complications.
肥胖和体脂肪分布是 2 型糖尿病和代谢综合征发展的重要危险因素。有证据表明,这种风险与不同脂肪沉积部位的脂肪细胞内在行为的差异有关。在目前的研究中,我们证明了从小鼠内脏和皮下白色脂肪组织中分离出来的脂肪前体细胞(APCs)具有不同的基因表达模式、分化潜力,以及对环境和遗传影响的反应。在经典诱导鸡尾酒的存在下,来源于皮下脂肪的 APC 很好地分化,而来源于内脏脂肪的 APC 分化不良,但可以通过添加骨形态发生蛋白(BMP)-2 或 BMP-4 来诱导分化。这种差异与皮下和内脏 APC 之间的基因表达特征存在显著差异相关。肥胖易感的 C57BL/6 小鼠中的 APC 数量高于肥胖抵抗的 129 小鼠,而暴露于高脂肪饮食的两种脂肪组织中的 APC 数量增加了高达 270%。因此,内脏和皮下脂肪组织中的 APC 是动态群体,它们在基因表达、分化特性以及对环境/遗传因素的反应方面存在内在差异。这些群体的调节可能为肥胖及其代谢并发症的治疗和预防提供新的靶点。