Hunan Institute of Animal & Veterinary Science, Changsha, 410131, People's Republic of China.
J Physiol Biochem. 2018 Aug;74(3):381-393. doi: 10.1007/s13105-018-0625-1. Epub 2018 Apr 13.
Differentiation of adipocytes and their aggregation to adipose tissue are critical for mammalian growth and development. MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs that play important roles in adipogenesis and lipid metabolism. miR-128-3p may contribute to adipose tissue development according to the previous studies. However, the role of miR-128-3p in the process of preadipocyte differentiation and lipid metabolism is not yet understood. The purpose of this research was to investigate the biological function and molecular mechanism of miR-128-3p in 3T3-L1 cells. In the present study, we found that miR-128-3p was downregulated during the process of 3T3-L1 preadipocyte differentiation. Overexpression of miR-128-3p obstructed the expressions of adipogenic marker genes as well as the lipid droplets accumulation and triglyceride content, suggesting the importance of miR-128-3p for adipogenesis. Moreover, miR-128-3p could lead to the retardation of cell proliferation in 3T3-L1 preadipocytes. Further evidences showed that, as a negative regulator of adipogenesis, miR-128-3p could directly target peroxisome proliferator-activated receptor γ (Pparg) which resulted in the suppression of 3T3-L1 preadipocyte differentiation, and miR-128-3p could also bind with SERTA domain containing 2 (Sertad2) which drove triglyceride hydrolysis and lipolysis. In addition, inhibition of Sertad2 with siRNA displayed the same effects as overexpression of miR-128-3p. Our research demonstrated that miR-128-3p impeded 3T3-L1 adipogenesis by targeting Pparg and Sertad2, resulting in the obstruction of preadipocyte differentiation and promotion of lipolysis. Taken together, this study offers profound insight into the mechanism of miRNA-mediated adipogenesis and lipid metabolism.
脂肪细胞的分化及其向脂肪组织的聚集对于哺乳动物的生长和发育至关重要。微小 RNA（miRNA）是一类内源性的小非编码 RNA，在脂肪生成和脂质代谢中发挥重要作用。根据之前的研究，miR-128-3p 可能有助于脂肪组织的发育。然而，miR-128-3p 在脂肪前体细胞分化和脂质代谢过程中的作用尚不清楚。本研究旨在探讨 miR-128-3p 在 3T3-L1 细胞中的生物学功能和分子机制。在本研究中，我们发现 miR-128-3p 在 3T3-L1 脂肪前体细胞分化过程中下调。miR-128-3p 的过表达抑制了脂肪生成标记基因的表达以及脂滴的积累和甘油三酯含量，表明 miR-128-3p 对脂肪生成很重要。此外，miR-128-3p 可导致 3T3-L1 脂肪前体细胞增殖减慢。进一步的证据表明，作为脂肪生成的负调节剂，miR-128-3p 可以直接靶向过氧化物酶体增殖物激活受体 γ（Pparg），从而抑制 3T3-L1 脂肪前体细胞分化，miR-128-3p 还可以与 SERTA 结构域包含蛋白 2（Sertad2）结合，促进甘油三酯水解和脂肪分解。此外，用 siRNA 抑制 Sertad2 可产生与过表达 miR-128-3p 相同的效果。我们的研究表明，miR-128-3p 通过靶向 Pparg 和 Sertad2 抑制 3T3-L1 脂肪生成，从而阻碍脂肪前体细胞分化并促进脂肪分解。总之，这项研究深入了解了 miRNA 介导的脂肪生成和脂质代谢的机制。
