Kim Soo M, Lun Mingyue, Wang Mei, Senyo Samuel E, Guillermier Christelle, Patwari Parth, Steinhauser Matthew L
Department of Medicine, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
National Resource for Imaging Mass Spectroscopy, Brigham and Women's Hospital, Cambridge, MA 02138, USA.
Cell Metab. 2014 Dec 2;20(6):1049-58. doi: 10.1016/j.cmet.2014.10.010. Epub 2014 Nov 20.
Fat mass expansion occurs by adipocyte hypertrophy or recruitment of differentiating adipocyte progenitors, the relative balance of which may impact systemic metabolism. We measured adipogenesis in murine subcutaneous (sWAT) and visceral white adipose tissue (vWAT) using stable isotope methodology and then modeled adipocyte turnover. Birth and death rates were similar within depots; however, turnover was higher in vWAT relative to sWAT. In juvenile mice, obesity increased adipogenesis, but in adults, this was only seen in vWAT after prolonged high-fat feeding. Statistical modeling suggests differentiation of adipocyte progenitors without an accompanying self-renewing division step may partially explain the age-dependent decline in hyperplastic potential. Additional metabolic interrogation of obese mice demonstrated an association between adipocyte turnover and insulin sensitivity. These data therefore identify adipocyte hypertrophy as the dominant mechanism of adult fat mass expansion and support the paradoxical concept that metabolic disease ensues due to a failure of adipose tissue plasticity.
脂肪量的增加通过脂肪细胞肥大或分化中的脂肪细胞祖细胞的募集而发生，两者的相对平衡可能会影响全身代谢。我们使用稳定同位素方法测量了小鼠皮下白色脂肪组织（sWAT）和内脏白色脂肪组织（vWAT）中的脂肪生成，然后对脂肪细胞更新进行建模。各脂肪库内的生成率和死亡率相似；然而，相对于sWAT，vWAT中的更新率更高。在幼年小鼠中，肥胖会增加脂肪生成，但在成年小鼠中，只有在长期高脂喂养后，vWAT中才会出现这种情况。统计模型表明，脂肪细胞祖细胞的分化没有伴随自我更新的分裂步骤，这可能部分解释了增生潜能随年龄增长而下降的现象。对肥胖小鼠的进一步代谢研究表明，脂肪细胞更新与胰岛素敏感性之间存在关联。因此，这些数据确定脂肪细胞肥大是成年期脂肪量增加的主要机制，并支持了一个看似矛盾的概念，即代谢性疾病是由于脂肪组织可塑性的丧失而导致的。
