当前位置: X-MOL 学术BBA Mol. Cell Res. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Tm7sf2 gene promotes adipocyte differentiation of mouse embryonic fibroblasts and improves insulin sensitivity
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2020-10-26 , DOI: 10.1016/j.bbamcr.2020.118897
Leonardo Gatticchi , Maya Petricciuolo , Paolo Scarpelli , Lara Macchioni , Lanfranco Corazzi , Rita Roberti

Adipogenesis is a finely orchestrated program involving a transcriptional cascade coordinated by CEBP and PPAR family members and by hormonally induced signaling pathways. Alterations in any of these factors result into impaired formation of fully differentiated adipocytes. Tm7sf2 gene encodes for a Δ(14)-sterol reductase primarily involved in cholesterol biosynthesis. Furthermore, TM7SF2 modulates the expression of the master gene of adipogenesis PPARγ, suggesting a role in the regulation of adipose tissue homeostasis. We investigated the differentiation of Tm7sf2−/− MEFs into adipocytes, compared to Tm7sf2+/+ MEFs. Tm7sf2 expression was increased at late stage of differentiation in wild type cells, while Tm7sf2−/− MEFs exhibited a reduced capacity to differentiate into mature adipocytes. Indeed, Tm7sf2−/− MEFs had lower neutral lipid accumulation and reduced expression of adipogenic regulators. At early stage, the reduction in C/EBPβ expression impaired mitotic clonal expansion, which is needed by preadipocytes for adipogenesis induction. At late stage, the expression and activity of C/EBPα and PPARγ were inhibited in Tm7sf2−/− cells, leading to the reduced expression of adipocyte genes like Srebp-1c, Fasn, Scd-1, Adipoq, Fabp4, and Glut4. Loss of the acquisition of adipocyte phenotype was accompanied by a reduction in the levels of Irs1, and phosphorylated Akt and ERK1/2, indicating a blunted insulin signaling in differentiating Tm7sf2−/− cells. Moreover, throughout the differentiation process, increased expression of the antiadipogenic Mmp3 was observed in MEFs lacking Tm7sf2. These findings indicate Tm7sf2 as a novel factor influencing adipocyte differentiation that could be relevant to adipose tissue development and maintenance of metabolic health.



中文翻译:

Tm7sf2基因促进小鼠胚胎成纤维细胞的脂肪细胞分化并提高胰岛素敏感性

脂肪形成是一个精心策划的程序,涉及由CEBP和PPAR家族成员以及激素诱导的信号通路协调的转录级联。这些因素中的任何一种改变都会导致完全分化的脂肪细胞形成受损。Tm7sf2基因编码主要参与胆固醇生物合成的Δ(14)-甾醇还原酶。此外,TM7SF2调节脂肪生成PPARγ主基因的表达,提示其在调节脂肪组织动态平衡中的作用。与Tm7sf2 + / + MEFs相比,我们研究了Tm7sf2 -/- MEFs向脂肪细胞的分化。在野生型细胞分化的后期,Tm7sf2表达增加,而Tm7sf2 -/- MEFs分化为成熟脂肪细胞的能力降低。实际上,Tm7sf2 -/- MEF具有较低的中性脂质蓄积和降低的成脂调节剂表达。在早期阶段,C /EBPβ表达的降低会损害有丝分裂克隆的扩增,这是前脂肪细胞诱导脂肪形成所必需的。在晚期阶段,C /EBPα和PPARγ在Tm7sf2 -/-细胞中的表达和活性受到抑制,导致Srebp-1cFasnScd-1AdipoqFabp4Glut4等脂肪细胞基因的表达减少。。脂肪细胞表型的获得性丧失伴随着Irs1以及磷酸化Akt和ERK1 / 2的水平降低,表明在分化Tm7sf2 -/-细胞中胰岛素信号的传导减弱。此外,在整个分化过程中,在缺乏Tm7sf2的MEF中观察到抗脂肪生成Mmp3的表达增加。这些发现表明,Tm7sf2是影响脂肪细胞分化的新因素,可能与脂肪组织的发育和代谢健康的维持有关。

更新日期:2020-11-02
down
wechat
bug