Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure
Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure
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DOI：
10.1073/pnas.0611568104
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发表时间：
2007-06-19
影响因子：
11.1
通讯作者：
Auwerx, Johan
中科院分区：
文献类型：
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作者：
Dali-Youcef, Nassim;Mataki, Chikage;Auwerx, Johan
肿瘤抑制因子视网膜母细胞瘤蛋白(PRB)在控制细胞周期、细胞凋亡和细胞分化中的作用已得到证实。最近，研究表明，在体外，缺乏pRb可以促进脂肪细胞从白色向棕色分化。我们使用Cre-Lox系统来特异性地灭活成人脂肪组织中的pRb。在高脂肪饮食下，pRb缺陷(pRb(ad-/-))小鼠由于能量消耗增加而未能增加体重。组织学、电子显微镜和基因表达研究证明，这种防止体重增加的作用是由于白色和棕色脂肪中线粒体活性的激活所致。此外，pRb(-/-)小鼠胚胎成纤维细胞的增殖率和凋亡率高于pRb(+/+)小鼠胚胎成纤维细胞，这可能是导致白色脂肪组织形态改变的原因之一。综上所述，我们的数据支持pRb在体内脂肪细胞命运决定中的直接作用，并提示pRb可能作为一个潜在的治疗靶点来触发白色脂肪组织和棕色脂肪组织中的线粒体激活，从而有利于增加能量消耗和随后的体重减轻。
The role of the tumor suppressor retinoblastoma protein (pRb) has been firmly established in the control of cell cycle, apoptosis, and differentiation. Recently, it was demonstrated that lack of pRb promotes a switch from white to brown adipocyte differentiation in vitro. We used the Cre-Lox system to specifically inactivate pRb in adult adipose tissue. Under a high-fat diet, pRb-deficient (pRb(ad-/-)) mice failed to gain weight because of increased energy expenditure. This protection against weight gain was caused by the activation of mitochondrial activity in white and brown fat as evidenced by histologic, electron microscopic, and gene expression studies. Moreover, pRb(-/-) mouse embryonic fibroblasts displayed higher proliferation and apoptosis rates than pRb(+/+) mouse embryonic fibroblasts, which could contribute to the altered white adipose tissue morphology. Taken together, our data support a direct role of pRb in adipocyte cell fate determination in vivo and suggest that pRb could serve as a potential therapeutic target to trigger mitochondrial activation in white adipose tissue and brown adipose tissue, favoring an increase in energy expenditure and subsequent weight loss.