Regulation of Alström syndrome gene expression during adipogenesis and its relationship with fat cell insulin sensitivity.
Regulation of Alström syndrome gene expression during adipogenesis and its relationship with fat cell insulin sensitivity.
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DOI：
10.3892/ijmm.21.6.731
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发表时间：
2008-06
影响因子：
5.4
通讯作者：
Sara Romano;G. Milan;C. Veronese;G. Collin;J. Marshall;C. Centobene;F. Favaretto;C. Dal Pra’;A. Scarda;S. Leandri;J. Naggert;P. Maffei;R. Vettor
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文献类型：
--
作者：
Sara Romano;G. Milan;C. Veronese;G. Collin;J. Marshall;C. Centobene;F. Favaretto;C. Dal Pra’;A. Scarda;S. Leandri;J. Naggert;P. Maffei;R. Vettor
Alström综合征（ALMS）是一种常染色体隐性遗传病，其表型特征包括多器官纤维化、胰岛素抵抗、肥胖和2型糖尿病。ALMS1是一种在ALMS患者中普遍表达的突变基因，可产生一种定位于纤毛细胞基底体和中心体的功能未知的蛋白质。与Bardet-Biedl综合征一起，ALMS是遗传性纤毛病的一员，但纤毛/中心体缺陷与代谢异常之间的联系仍有待确定。在这项研究中，我们首次量化了Alms1在3T3-L1细胞分化过程中脂肪形成的细胞模型中的表达。在前脂肪细胞向脂肪细胞转化的过程中，观察到Alms1 mRNA的早期减少。然而，用成脂因子急性治疗前脂肪细胞，并没有导致Alms1表达的显著变化。此外，为了研究Alms1与脂肪细胞胰岛素敏感程度之间的可能关系，我们用胰岛素依赖性2-[1-3H]-脱氧葡萄糖摄取法评估，我们分别用胰岛素或罗格列酮慢性治疗诱导3T3-L1脂肪细胞胰岛素敏感性的降低或增加。在所有这些条件下，Alms1的表达保持不变。总之，我们的研究结果表明，Alms1在脂肪前细胞中表达水平较高，表明该基因在脂肪形成的早期阶段发挥作用。此外，脂肪细胞胰岛素敏感性的变化并不意味着对Alms1表达有任何影响。
Alström syndrome (ALMS) is an autosomal recessive genetic disease with characteristic phenotypical features including multi-organ fibrosis, insulin resistance, obesity and type 2 diabetes. ALMS1, a ubiquitously expressed gene mutated in ALMS patients, gives rise to a protein of unknown function localized to basal bodies of ciliated cells and centrosomes. Together with Bardet-Biedl syndrome, ALMS is a member of genetic ciliopathies, but the link between cilia/centrosome deficits and metabolic abnormalities remains to be determined. In this study for the first time we quantified Alms1 expression in a cellular model of adipogenesis during the differentiation of 3T3-L1 cells. An early decrease in Alms1 mRNA was observed during preadipocyte to adipocyte conversion. However, acute treatment of preadipocytes with the adipogenic factors did not result in significant change of Alms1 expression. In addition, to study the possible relationship between Alms1 and the degree of fat cell insulin sensitivity, as assessed with an insulin-dependent 2-[1-3H]-deoxyglucose uptake assay, we induced either a reduction or an increase in 3T3-L1 adipocytes insulin sensitivity by a chronic treatment with insulin or rosiglitazone respectively. In all these conditions Alms1 expression remained unchanged. In conclusion, our results show that Alms1 is expressed at higher level in preadipocytes suggesting a role of the gene in the early phase of adipogenesis. Moreover, changes in fat cell insulin sensitivity do not imply any effect on Alms1 expression.