Laboratory of Molecular Biology and Immunology, NIA-IRP, NIH, Baltimore, Maryland 21224, USA.
Mol Cell Biol. 2011 Feb;31(4):626-38. doi: 10.1128/MCB.00894-10. Epub 2010 Dec 6.
Adipose tissue development is tightly regulated by altering gene expression. MicroRNAs are strong posttranscriptional regulators of mammalian differentiation. We hypothesized that microRNAs might influence human adipogenesis by targeting specific adipogenic factors. We identified microRNAs that showed varying abundance during the differentiation of human preadipocytes into adipocytes. Among them, miR-130 strongly affected adipocyte differentiation, as overexpressing miR-130 impaired adipogenesis and reducing miR-130 enhanced adipogenesis. A key effector of miR-130 actions was the protein peroxisome proliferator-activated receptor γ (PPARγ), a major regulator of adipogenesis. Interestingly, miR-130 potently repressed PPARγ expression by targeting both the PPARγ mRNA coding and 3' untranslated regions. Adipose tissue from obese women contained significantly lower miR-130 and higher PPARγ mRNA levels than that from nonobese women. Our findings reveal that miR-130 reduces adipogenesis by repressing PPARγ biosynthesis and suggest that perturbations in this regulation is linked to human obesity.
脂肪组织的发育是通过改变基因表达来严格调控的。microRNAs 是哺乳动物分化的强有力的转录后调控因子。我们假设 microRNAs 可能通过靶向特定的脂肪生成因子来影响人类脂肪生成。我们鉴定了在人前体脂肪细胞分化为脂肪细胞过程中表达丰度不同的 microRNAs。其中,miR-130 强烈影响脂肪细胞分化,过表达 miR-130 会损害脂肪生成,而降低 miR-130 则增强脂肪生成。miR-130 作用的关键效应因子是过氧化物酶体增殖物激活受体 γ(PPARγ),它是脂肪生成的主要调节因子。有趣的是,miR-130 通过靶向 PPARγ mRNA 编码区和 3'非翻译区,强烈抑制 PPARγ 的表达。与非肥胖女性相比,肥胖女性的脂肪组织中 miR-130 水平显著降低,而 PPARγ mRNA 水平显著升高。我们的研究结果表明,miR-130 通过抑制 PPARγ 生物合成来减少脂肪生成,并提示这种调节的紊乱与人类肥胖有关。