The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function
The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function
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DOI：
10.1096/fj.201701216r
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发表时间：
2018-07-01
期刊：
影响因子：
4.8
通讯作者：
Leibel, Rudolph L.
中科院分区：
文献类型：
--
作者：
Carli, Jayne F. Martin;LeDuc, Charles A.;Leibel, Rudolph L.
FTO（-酮戊二酸依赖性双加氧酶）基因内的遗传变异与食物摄入增加导致的肥胖适度增加密切相关。这些风险等位基因与FTO和邻近的RPGRIP 1 L（视网膜色素变性GTTRIP 1调节因子相互作用蛋白1样）的表达降低相关。RPGRIP 1 L编码一种对初级纤毛功能至关重要的蛋白质，初级纤毛将细胞外信息传递给细胞。Rpgrip 1 l（+/-）小鼠表现出增加的肥胖，部分是由于摄食过多。在这里，我们描述了Rpgrip 1 l在脂肪细胞中的作用，这可能有助于在这些动物中观察到的肥胖表型，并可能在FTO风险等位基因分离的人类中观察到。3 T3-L1前脂肪细胞中Rpgrip 1 l的缺失增加了能够分化为成熟脂肪细胞的细胞数量。使用Adipoq-Cre敲除成熟脂肪细胞中的Rpgrip 1 l不会增加喂食食物或高脂饮食的小鼠的肥胖。我们也没有观察到Rpgrip 1 l敲低对成熟3 T3-L1脂肪细胞的任何影响。因此，在某种程度上，Rpgrip 1 l影响细胞自主脂肪组织的功能，它可能会这样做的结果，在前脂肪细胞，其中初级纤毛是功能上重要的效果传达。我们提出，在分离FTO肥胖风险等位基因的人中，前脂肪细胞中RPGRIP 1 L表达的降低可能增加脂肪组织的储存能力。勒杜克角一、张玉，Stratigopoulos，G.，莱贝尔河L. Rpgrip 1 l是初级纤毛的一个组成部分，在脂肪细胞发育和功能中的作用。
Genetic variants within the FTO (-ketoglutarate-dependent dioxygenase) gene have been strongly associated with a modest increase in adiposity as a result of increased food intake. These risk alleles are associated with decreased expression of both FTO and neighboring RPGRIP1L (retinitis pigmentosa GTPase regulator-interacting protein 1 like). RPGRIP1L encodes a protein that is critical to the function of the primary cilium, which conveys extracellular information to the cell. Rpgrip1l(+/-) mice exhibit increased adiposity, in part, as a result of hyperphagia. Here, we describe the effects of Rpgrip1l in adipocytes that may contribute to the adiposity phenotype observed in these animals and possibly in humans who segregate for FTO risk alleles. Loss of Rpgrip1l in 3T3-L1 preadipocytes increased the number of cells that are capable of differentiating into mature adipocytes. Knockout of Rpgrip1l in mature adipocytes using Adipoq-Cre did not increase adiposity in mice that were fed chow or a high-fat diet. We also did not observe any effects of Rpgrip1l knockdown in mature 3T3-L1 adipocytes. Thus, to the extent that Rpgrip1l affects cell-autonomous adipose tissue function, it may do so as a result of the effects conveyed in preadipocytes in which the primary cilium is functionally important. We propose that decreased RPGRIP1L expression in preadipocytes in humans who segregate for FTO obesity risk alleles may increase the storage capacity of adipose tissue.Martin Carli, J. F., LeDuc, C. A., Zhang, Y., Stratigopoulos, G., Leibel, R. L. The role of Rpgrip1l, a component of the primary cilium, in adipocyte development and function.