Impairment of primary cilia contributes to visceral adiposity of high fat diet‐fed mice
Impairment of primary cilia contributes to visceral adiposity of high fat diet‐fed mice
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DOI：
10.1002/jcb.26253
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发表时间：
2018-02
影响因子：
4
通讯作者：
Ni Qiu;Wei-jin Fang;Hong-Sheng Li;Zhi-min He;Zhou-sheng Xiao;Y. Xiong
中科院分区：
文献类型：
--
作者：
Ni Qiu;Wei-jin Fang;Hong-Sheng Li;Zhi-min He;Zhou-sheng Xiao;Y. Xiong
敲除驱动蛋白家族成员3A（Kif 3a）在成熟成骨细胞中的初级纤毛形成缺陷导致骨质减少和脂肪生成增强。脂肪生成在高脂饮食（HFD）诱导的肥胖引起的脂肪组织扩张中起重要作用。初级纤毛是否参与高脂饮食诱导的肥胖仍不清楚。在这项研究中，我们发现，初级纤毛的数量和长度以及KIF 3A和鞭毛内转运88同源物（IFFT 88）mRNA和蛋白质的表达水平在脂肪形成的第3天达到峰值，然后在第9天下降至低基础表达水平，当分化为来自瘦小鼠的VAT-SVF中的脂质积累脂肪细胞时。通过shRNA和化学方法减少了初级纤毛的数量，导致Pparγ，Cebp-α，Srebp-1和Fasn的转录物以及PPARγ和Fasn的蛋白水平升高。与通过抑制对照VAT-SVF中初级纤毛形成的促脂肪形成作用相似，HFD导致VAT-SVF培养物中初级纤毛形成严重减少和脂肪形成增强。流式细胞术分析显示，通过用shRNA或化学方法敲低初级纤毛，对照VAT-SVFs中G2/M期细胞的百分比以及Cyclin A2和CDK 2的蛋白表达增加，并且HFD诱导肥胖VAT-SVFs。因此，原纤毛的表达与成脂分化呈负相关。HFD导致VAT-SVF中初级纤毛的严重缺陷，通过在脂肪形成的早期阶段促进细胞周期重新进入来增强脂肪形成，从而导致脂肪组织扩张。
Deficiency of primary cilia formation by knockout kinesin family member 3A (Kif3a) in mature osteoblasts led to osteopenia and enhanced adipogenesis. Adipogenesis plays an important role in adipose tissue expansion by High‐fat‐diet (HFD) induced obesity. Whether primary cilia participate in high‐fat‐diet induced adiposity remains unclear. In this study, we found that the number and length of primary cilia and expression levels of KIF3A and intraflagellar transport 88 homolog (IFT88) mRNA and proteins reached peak on the day 3 of adipogenesis, followed by a decrease to reach low basal expression levels at day 9 when differentiated to lipid accumulating adipocytes in VAT‐SVFs derived from lean mice. The number of primary cilia was reduced by shRNA and chemical methods, leading to elevated transcripts of Pparγ, Cebp‐α, Srebp‐1, and Fasn and protein levels of PPARγ and FASN. Similar to the proadipogenic effect by the inhibition of primary cilia formation in control VAT‐SVFs, HFD caused severe reduction of primary cilia formation and enhancement of adipogenesis in VAT‐SVFs cultures. Flow cytometry analysis revealed percentage of G2/M phase cells and the protein expression of Cyclin A2 and CDK2 increased in control VAT‐SVFs by knockdown of primary cilia with shRNA or chemical methods and HFD induced obese VAT‐SVFs. In conclusion, the expression of primary cilia was in reverse correlation with adipogenic differentiation. HFD caused severe defects of primary cilia in VAT‐SVFs, leading to adipose tissue expansion by enhancement of adipogenesis through promoting cell cycle re‐entry at the early stage of adipogenesis.