Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4.

Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4.
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DOI:
10.3389/fendo.2021.750261
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发表时间:
2021
影响因子:
5.2
通讯作者:
Wada J
Wada J
中科院分区:
医学2区
文献类型:
--
作者:
Yamaguchi S;Zhang D;Katayama A;Kurooka N;Sugawara R;Albuayjan HHH;Nakatsuka A;Eguchi J;Wada J

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脂肪细胞中表达的microRNA参与肥胖症中靶mRNA的转录调控,但关键参与这一过程的miRNAs尚未得到很好的表征。在此,我们通过RNA测序鉴定了高脂高糖(HFHS)饲料喂养的C57 BL/6小鼠白色脂肪组织中miR-221- 3 p和miR-222- 3 p的上调。Mir 221和Mir 222是旁系同源基因,并且共享共同的种子序列,并且与Mir 221/222 flox/y相比,用HFHS食物喂养的Mir 221/222 AdipoKO小鼠表现出对肥胖发展的抗性。Ddit 4是Mir 221和Mir 222的直接靶点,并且在Mir 221/222 AdipoKO中Ddit 4的上调与TSC 2(结节性硬化症复合物2)/哺乳动物雷帕霉素靶蛋白复合物1(mTORC 1)/S6 K(核糖体蛋白S6激酶)途径的抑制有关。miR-222- 3 p的过表达与脂肪生成的增强有关,它可能是基于miRNA的治疗的潜在候选者。
MicroRNAs expressed in adipocytes are involved in transcriptional regulation of target mRNAs in obesity, but miRNAs critically involved in this process is not well characterized. Here, we identified upregulation of miR-221-3p and miR-222-3p in the white adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir221 and Mir222 are paralogous genes and share the common seed sequence and Mir221/222AdipoKO mice fed with HFHS chow demonstrated resistance to the development of obesity compared with Mir221/222flox/y . Ddit4 is a direct target of Mir221 and Mir222, and the upregulation of Ddit4 in Mir221/222AdipoKO was associated with the suppression of TSC2 (tuberous sclerosis complex 2)/mammalian target of rapamycin complex 1 (mTORC1)/S6K (ribosomal protein S6 kinase) pathway. The overexpression of miR-222-3p linked to enhanced adipogenesis, and it may be a potential candidate for miRNA-based therapy.
抑制肝脏中IRS-1表达的microRNA鉴定。
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