Daquinag A C, Tseng C, Salameh A, Zhang Y, Amaya-Manzanares F, Dadbin A, Florez F, Xu Y, Tong Q, Kolonin M G
Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, TX, USA.
Cell Death Differ. 2015 Feb;22(2):351-63. doi: 10.1038/cdd.2014.148. Epub 2014 Oct 24.
Overgrowth of white adipose tissue (WAT) in obesity occurs as a result of adipocyte hypertrophy and hyperplasia. Expansion and renewal of adipocytes relies on proliferation and differentiation of white adipocyte progenitors (WAP); however, the requirement of WAP for obesity development has not been proven. Here, we investigate whether depletion of WAP can be used to prevent WAT expansion. We test this approach by using a hunter-killer peptide designed to induce apoptosis selectively in WAP. We show that targeted WAP cytoablation results in a long-term WAT growth suppression despite increased caloric intake in a mouse diet-induced obesity model. Our data indicate that WAP depletion results in a compensatory population of adipose tissue with beige adipocytes. Consistent with reported thermogenic capacity of beige adipose tissue, WAP-depleted mice display increased energy expenditure. We conclude that targeting of white adipocyte progenitors could be developed as a strategy to sustained modulation of WAT metabolic activity.
肥胖症中白色脂肪组织（WAT）过度生长是脂肪细胞肥大和增生的结果。脂肪细胞的扩张和更新依赖于白色脂肪祖细胞（WAP）的增殖和分化；然而，WAP对肥胖症发展的必要性尚未得到证实。在此，我们研究是否可以通过消耗WAP来预防WAT扩张。我们通过使用一种设计用于在WAP中选择性诱导凋亡的猎杀肽来测试这种方法。我们表明，在小鼠饮食诱导的肥胖模型中，尽管热量摄入增加，但靶向WAP细胞消融导致长期的WAT生长抑制。我们的数据表明，WAP消耗导致脂肪组织中米色脂肪细胞的代偿性增加。与报道的米色脂肪组织的产热能力一致，WAP消耗的小鼠表现出能量消耗增加。我们得出结论，靶向白色脂肪祖细胞可作为一种持续调节WAT代谢活性的策略来开发。
