Animal Bioscience

Asian Australasian Association of Animal Production Societies (아세아태평양축산학회)
권호 표지
DOI QR코드

DOI QR Code

Bta-miR-365-3p-targeted FK506-binding protein 5 participates in the AMPK/mTOR signaling pathway in the regulation of preadipocyte differentiation in cattle

  • Mengdi Chen (College of Agriculture, Yanbian University) ;
  • Congcong Zhang (Institute of Animal Science, Jilin Academy of Agricultural Science) ;
  • Zewen Wu (College of Agriculture, Yanbian University) ;
  • Siwei Guo (College of Agriculture, Yanbian University) ;
  • Wenfa Lv (Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University) ;
  • Jixuan Song (College of Agriculture, Yanbian University) ;
  • Beibei Hao (College of Agriculture, Yanbian University) ;
  • Jinhui Bai (College of Agriculture, Yanbian University) ;
  • Xinxin Zhang (College of Agriculture, Yanbian University) ;
  • Hongyan Xu (College of Agriculture, Yanbian University) ;
  • Guangjun Xia (College of Agriculture, Yanbian University)
  • Received : 2023.08.29
  • Accepted : 2024.02.18
  • Published : 2024.07.01
Download PDF
⟨ Previous Next ⟩

Abstract

Objective: MicroRNAs (miRNAs) are endogenous non-coding RNAs that can play a role in the post-transcriptional regulation of mammalian preadipocyte differentiation. However, the precise functional mechanism of its regulation of fat metabolism is not fully understood. Methods: We identified bta-miR-365-3p, which specifically targets the 3' untranslated region (3'UTR) of the FK506-binding protein 5 (FKBP5), and verified its mechanisms for regulating expression and involvement in adipogenesis. Results: In this study, we found that the overexpression of bta-miR-365-3p significantly decreased the lipid accumulation and triglyceride content in the adipocytes. Compared to inhibiting bta-miR-36 5-3p group, overexpression of bta-miR-365-3p can inhibit the expression of adipocyte differentiation-related genes C/EBPα and PPARγ. The dual-luciferase reporter system further validated the targeting relationship between bta-miR-365-3p and FKBP5. FKBP5 mRNA and protein expression were detected by quantitative real-time polymerase chain reaction and Western blot. Overexpression of bta-miR-365-3p significantly down-regulated FKBP5 expression, while inhibition of bta-miR-365-3p showed the opposite, indicating that bta-miR-365-3p negatively regulates FKBP5. Adenosine 5'-monophosphate (AMP)-activated protein kinase/mammalian target of rapamycin (AMPK/mTOR) signaling pathway is closely related to the regulation of cell growth and is involved in the development of bovine adipocytes. In this study, overexpression of bta-miR-365-3p significantly inhibited mRNA and protein expression of AMPK, mTOR, and SREBP1 genes, while the inhibition of bta-miR-365-3p expression was contrary to these results. Overexpression of FKBP5 significantly upregulated AMPK, mTOR, and SREBP1 gene expression, while inhibition of FKBP5 expression was contrary to the above experimental results. Conclusion: In conclusion, these results indicate that bta-miR-365-3p may be involved in the AMPK/mTOR signaling pathway in regulating Yanbian yellow cattle preadipocytes differentiation by targeting the FKBP5 gene.

Keywords

Acknowledgement

This research was funded by National Natural Science Foundation of China, grant number 32160774, the Science and Technology Development Plan of Jilin Province of China, grant number YDZ J202203C G ZH 037, Jilin Science and Technology Development Plan, grant number 20200402053 NC, Yanbian University School-Enterprise Cooperation Project, grant number Yanda Kehezi (2019) No.1 and National Key R&D Program of China 2021YFD1200400.

References

  1. Hoehne A, Nuernberg G, Kuehn C, Nuernberg K. Relationships between intramuscular fat content, selected carcass traits, and fatty acid profile in bulls using a F2-population. Meat Sci 2012;90:629-35. https://doi.org/10.1016/j.meatsci.2011.10.005 
  2. Stewart SM, Gardner GE, Mcgilchrist P, et al. Prediction of consumer palatability in beef using visual marbling scores and chemical intramuscular fat percentage. Meat Sci 2020;181:108322. https://doi.org/10.1016/j.meatsci.2020.108322 
  3. Baik M, Kang HJ, Park SJ, et al. Triennial growth and development symposium: molecular mechanisms related to bovine intramuscular fat deposition in the longissimus muscle. J Anim Sci 2017;95:2284-303. https://doi.org/10.2527/jas.2016.1160 
  4. Yan CG, Wang Y, Piao SZ, Piao XX, Piao HL, Li WB. Study on the beef quality traits of Yanbian cattle. J Yellow Cattle Sci 2004;30:5-7. 
  5. Dani C, Smith AG, Dessolin S, et al. Differentiation of embryonic stem cells into adipocytes in vitro. J Cell Sci 1997;110:1279-85. https://doi.org/10.1242/jcs.110.11.1279 
  6. Ali AT, Hochfeld WE, Myburgh R, Pepper MS. Adipocyte and adipogenesis. Eur J Cell Biol 2013;92:229-36. https://doi.org/10.1016/j.ejcb.2013.06.001 
  7. Mota de Sa P, Richard AJ, Hang H, Stephens JM. Transcriptional regulation of adipogenesis. Compr Physiol 2017;7:635-74. https://doi.org/10.1002/cphy.c160022 
  8. Wu Z, Rosen ED, Brun R, et al. Cross-regulation of C/EBP alpha and PPAR gamma controls the transcriptional pathway of adipogenesis and insulin sensitivity. Mol Cell 1999;3:151-8. https://doi.org/10.1016/s1097-2765(00)80306-8 
  9. Liu KS, Tong H, Li TP, Wang XD, Chen YJ. Research progress in molecular biology related quantitative methods of MicroRNA. Am J Transl Res 2020;12:3198-211. 
  10. Olena AF, Patton JG. Genomic organization of microRNAs. J Cell Physiol 2010;222:540-5. https://doi.org/10.1002/jcp.21993 
  11. Esau C, Kang X, Peralta E, et al. MicroRNA-143 regulates adipocyte differentiation. J Biol Chem 2004;279:52361-5. https://doi.org/10.1074/jbc.c400438200 
  12. Xu H, Shao J, Fang J, et al. miR-381Targets KCTD15 to regulate bovine preadipocyte differentiation in vitro. Horm Metab Res 2021;53:63-70. https://doi.org/10.1055/a-1276-1602 
  13. Ma XY, Wei DW, Cheng G, et al. Bta-miR-130a/b regulates preadipocyte differentiation by targeting PPARG and CYP2U1 in beef cattle. Mol Cell Probes 2018;42:10-7. https://doi.org/10.1016/j.mcp.2018.10.002 
  14. Chen L, Chen YW, Zhang S, et al. MiR-540 as a novel adipogenic inhibitor impairs adipogenesis via suppression of PPARγ. J Cell Biochem 2015;116:969-76. https://doi.org/10.1002/jcb.25050 
  15. Xia GJ. Screening of candidate genes associated to meat quality traits of Yanbian yellow cattle by a combination of miRNA and functional genes transcriptome [doctoral dissertation]. Yanji, China: Yanbian University; 2014. 
  16. Jin WW, Grant JR, Stothard P, Moore SS, Guan LL. Characterization of bovine miRNAs by sequencing and bioinformatics analysis. BMC Mol Biol 2009;10:90. https://doi.org/10.1186/1471-2199-10-90 
  17. Muroya S, Taniguchi M, Shibata M, et al. Profiling of differentially expressed microRNA and the bioinformatic target gene analyses in bovine fast- and slow-type muscles by massively parallel sequencing. J Anim Sci 2013;91:90-130. https://doi.org/10.2527/jas.2012-5371 
  18. Zhang WW, Sun XF, Tong HL, et al. Effect of differentiation on microRNA expression in bovine skeletal muscle satellite cells by deep sequencing. Cell Mol Biol Lett 2016;21:8. https://doi.org/10.1186/s11658-016-0009-x 
  19. Sarjeant K, Stephens JM. Adipogenesis. Cold Spring Harb Perspect Biol 2012;4:a008417. https://doi.org/10.1101/cshperspect.a008417 
  20. Xi FX, Wei CS, Xu YT, et al. MicroRNA-214-3p targeting Ctnnb1 promotes 3T3-L1 preadipocyte diferentiation by interfering with the Wnt/β-Catenin signaling pathway. Int J Mol Sci 2019;20:1816. https://doi.org/10.3390/ijms20081816 
  21. Sun GR, Li F, Ma XF, et al. gga-miRNA-18b-3p inhibits intramuscular adipocytes differentiation in chicken by targeting the ACOT13 gene. Cells 2019;8:556. https://doi.org/10.3390/cells8060556 
  22. Li B, Huang XY, Yang C, et al. miR-27a regulates sheep adipocyte differentiation by targeting CPT1B gene. Animals (Basel) 2021;12:28. https://doi.org/10.3390/ani12010028 
  23. Zhang Z, Gao Y, Xu MQ, et al. miR-181a regulate porcine preadipocyte differentiation by targeting TGFBR1. Gene 2019;681:45-51. https://doi.org/10.1016/j.gene.2018.09.046 
  24. Yin CG, Shao J, Yin BZ, Jiao S, Xia GJ. Effect of castration on fatty deposition and the expression of related Genesin Yanbian yellow cattle (in Chinese with English abstract). J Northeast Agric Sci 2019;44:44-8. 
  25. Hubler TR, Scammell JG. Intronic hormone response elements mediate regulation of FKBP5 by progestins and glucocorticoids. Cell Stress Chaperones 2004;9:243-52. https://doi.org/10.1379/csc-32r.1 
  26. Stechschulte LA, Qiu B, Warrier M, et al. FKBP51 null mice are resistant to diet-induced obesity and the PPARγ agonist rosiglitazone. Endocrinology 2016;157:3888-900. https://doi.org/10.1210/en.2015-1996 
  27. Stechschulte LA, Sanchez ER. FKBP51-a selective modulator of glucocorticoid and androgen sensitivity. Curr Opin Pharmacol 2011;11:332-7. https://doi.org/10.1016/j.coph.2011.04.012 
  28. Han JB, Wang YG. mTORC1 signaling in hepatic lipid metabolism. Protein Cell 2018;9:145-51. https://doi.org/10.1007/s13238-017-0409-3 
  29. Yang ZF, Klionsky DJ. An overview of the molecular mechanism of autophagy. Curr Top Microbiol Immunol 2009;335:1-32. https://doi.org/10.1007/978-3-642-00302-8_1 
  30. Huang YJ, Xie LS. mTOR signal pathway research progress in nutrition environment energy metabolism (in Chinese with English abstract). Chin J Clin Res 2020;33:244-8.