Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes.

Impaired adipogenesis and lipolysis in the mouse upon selective ablation of the retinoid X receptor alpha mediated by a tamoxifen-inducible chimeric Cre recombinase (Cre-ERT2) in adipocytes.
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DOI:
10.1073/pnas.98.1.224
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发表时间:
2001-01
影响因子:
11.1
通讯作者:
T. Imai;Ming Jiang;P. Chambon;D. Metzger
T. Imai;Ming Jiang;P. Chambon;D. Metzger
中科院分区:
综合性期刊1区
文献类型:
--
作者:
T. Imai;Ming Jiang;P. Chambon;D. Metzger

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视黄酮X受体α (rxrα)作为多种核受体的异二聚体,参与多种信号通路。为了研究其在能量稳态中的功能,我们使用他莫昔芬诱导的Cre-ERT2重组系统选择性地切除了4周龄转基因小鼠脂肪细胞中的rxrα基因。脂肪细胞中缺乏rxrα的小鼠对饮食和化学诱导的肥胖有抵抗力,并且在禁食诱导的脂肪分解中受损。我们的结果也表明RXRalpha参与脂肪细胞分化。因此,我们的数据证明了脂肪细胞选择性暂时控制基因工程的可行性,并揭示了rxrα在脂肪形成中的核心作用,可能是过氧化物酶体增殖体激活受体γ的异二聚体伴侣。
Retinoid X receptor alpha (RXRalpha) is involved in multiple signaling pathways, as a heterodimeric partner of several nuclear receptors. To investigate its function in energy homeostasis, we have selectively ablated the RXRalpha gene in adipocytes of 4-week-old transgenic mice by using the tamoxifen-inducible Cre-ERT2 recombination system. Mice lacking RXRalpha in adipocytes were resistant to dietary and chemically induced obesity and impaired in fasting-induced lipolysis. Our results also indicate that RXRalpha is involved in adipocyte differentiation. Thus, our data demonstrate the feasibility of adipocyte-selective temporally controlled gene engineering and reveal a central role of RXRalpha in adipogenesis, probably as a heterodimeric partner for peroxisome proliferator-activated receptor gamma.