Flynn Edward J, Trent Chad M, Rawls John F
Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, NC 27599-7545, USA.
J Lipid Res. 2009 Aug;50(8):1641-52. doi: 10.1194/jlr.M800590-JLR200. Epub 2009 Apr 14.
The global obesity epidemic demands an improved understanding of the developmental and environmental factors regulating fat storage. Adipocytes serve as major sites of fat storage and as regulators of energy balance and inflammation. The optical transparency of developing zebrafish provides new opportunities to investigate mechanisms governing adipocyte biology, however zebrafish adipocytes remain uncharacterized. We have developed methods for visualizing zebrafish adipocytes in vivo by labeling neutral lipid droplets with Nile Red. Our results establish that neutral lipid droplets first accumulate in visceral adipocytes during larval stages and increase in number and distribution as zebrafish grow. We show that the cellular anatomy of zebrafish adipocytes is similar to mammalian white adipocytes and identify peroxisome-proliferator activated receptor gamma and fatty acid binding protein 11a as markers of the zebrafish adipocyte lineage. By monitoring adipocyte development prior to neutral lipid deposition, we find that the first visceral preadipocytes appear in association with the pancreas shortly after initiation of exogenous nutrition. Zebrafish reared in the absence of food fail to form visceral preadipocytes, indicating that exogenous nutrition is required for adipocyte development. These results reveal homologies between zebrafish and mammalian adipocytes and establish the zebrafish as a new model for adipocyte research.
全球肥胖流行要求我们更好地理解调节脂肪储存的发育和环境因素。脂肪细胞是脂肪储存的主要场所,也是能量平衡和炎症的调节者。发育中的斑马鱼具有光学透明性,这为研究脂肪细胞生物学调控机制提供了新机会,然而斑马鱼脂肪细胞的特征仍未明确。我们已开发出通过用尼罗红标记中性脂滴来在体内可视化斑马鱼脂肪细胞的方法。我们的结果表明,中性脂滴在幼体阶段首先在内脏脂肪细胞中积累,并且随着斑马鱼生长,其数量和分布增加。我们发现斑马鱼脂肪细胞的细胞解剖结构与哺乳动物白色脂肪细胞相似,并鉴定出过氧化物酶体增殖物激活受体γ和脂肪酸结合蛋白11a作为斑马鱼脂肪细胞谱系的标志物。通过在中性脂沉积之前监测脂肪细胞发育,我们发现最早的内脏前脂肪细胞在开始外源营养后不久与胰腺相关出现。在没有食物的情况下饲养的斑马鱼无法形成内脏前脂肪细胞,这表明脂肪细胞发育需要外源营养。这些结果揭示了斑马鱼和哺乳动物脂肪细胞之间的同源性,并将斑马鱼确立为脂肪细胞研究的新模型。