Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice
Human brown adipose tissue is phenocopied by classical brown adipose tissue in physiologically humanized mice
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DOI：
10.1038/s42255-019-0101-4
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发表时间：
2019-08-01
影响因子：
20.8
通讯作者：
Petrovic, Natasa
中科院分区：
文献类型：
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作者：
de Jong, Jasper M. A.;Sun, Wenfei;Petrovic, Natasa
人和啮齿类动物棕色脂肪组织（BAT）在形态和分子上存在差异。在这里，我们将人类BAT与“生理人源化”小鼠的经典棕色和白色/米色脂肪组织进行了比较：在接近人类热量和营养条件下生活的中年小鼠，即长时间暴露于热中性温度（约30摄氏度）和高能量（高脂肪、高糖）饮食。我们发现，这些生理人源化小鼠的经典棕色脂肪的形态、细胞和分子特征（包括标记和脂肪选择基因表达）与人类BAT明显相似，而不是白/米色脂肪。我们还通过计算机和实验证明，在生理性人源化小鼠中，只有经典BAT具有高产热潜能。这些观察结果表明，经典的啮齿动物BAT是转化研究的首选组织，旨在招募人类BAT来对抗肥胖及其合并症的发展。
Human and rodent brown adipose tissues (BAT) appear morphologically and molecularly different. Here we compare human BAT with both classical brown and brite/beige adipose tissues of 'physiologically humanized' mice: middle-aged mice living under conditions approaching human thermal and nutritional conditions, that is, prolonged exposure to thermoneutral temperature (approximately 30 degrees C) and to an energy-rich (high-fat, high-sugar) diet. We find that the morphological, cellular and molecular characteristics (both marker and adipose-selective gene expression) of classical brown fat, but not of brite/beige fat, of these physiologically humanized mice are notably similar to human BAT. We also demonstrate, both in silico and experimentally, that in physiologically humanized mice only classical BAT possesses a high thermogenic potential. These observations suggest that classical rodent BAT is the tissue of choice for translational studies aimed at recruiting human BAT to counteract the development of obesity and its comorbidities.