DOI QR코드

DOI QR Code

The cooperative regulatory effect of the miRNA-130 family on milk fat metabolism in dairy cows

  • Xiaofen Li (School of Animal Science and Technology, Jiangsu Agri-animal Husbandry Vocational College) ;
  • Yanni Wu (College of Animal Science and Technology, Yangzhou University) ;
  • Xiaozhi Yang (School of Animal Science and Technology, Jiangsu Agri-animal Husbandry Vocational College) ;
  • Rui Gao (College of Animal Science and Technology, Yangzhou University) ;
  • Qinyue Lu (Laboratory of Animal Developmental Biology, Department of Animal Science, Chungbuk National University) ;
  • Xiaoyang Lv (Joint International Research Laboratory of Agriculture & Agri-Product Safety, Ministry of Education, Yangzhou University) ;
  • Zhi Chen (College of Animal Science and Technology, Yangzhou University)
  • Received : 2023.11.15
  • Accepted : 2024.03.02
  • Published : 2024.07.01

Abstract

Objective: There is a strong relationship between the content of beneficial fatty acids in milk and milk fat metabolic activity in the mammary gland. To improve milk quality, it is therefore necessary to study fatty acid metabolism in bovine mammary gland tissue. In adipose tissue, peroxisome proliferator-activated receptor gamma (PPARG), the core transcription factor, regulates the fatty acid metabolism gene network and determines fatty acid deposition. However, its regulatory effects on mammary gland fatty acid metabolism during lactation have rarely been reported. Methods: Transcriptome sequencing was performed during the prelactation period and the peak lactation period to examine mRNA expression. The significant upregulation of PPARG drew our attention and led us to conduct further research. Results: According to bioinformatics prediction, dual-luciferase reporter system detection, real-time quantitative reverse transcription polymerase chain reaction and Western blotting, miR-130a and miR-130b could directly target PPARG and inhibit its expression. Furthermore, triglyceride and oil red O staining proved that miR-130a and miR-130b inhibited milk fat metabolism in bovine mammary epithelial cells (BMECs), while PPARG promoted this metabolism. In addition, we also found that the coexpression of miR-130a and miR-130b significantly enhanced their ability to regulate milk fat metabolism. Conclusion: In conclusion, our findings indicated that miR-130a and miR-130b could target and repress PPARG and that they also have a functional superposition effect. miR-130a and miR-130b seem to synergistically regulate lipid catabolism via the control of PPARG in BMECs. In the long-term, these findings might be helpful in developing practical means to improve high-quality milk.

Keywords

Acknowledgement

This study was supported by Taizhou Science and Technology Support Plan (Agriculture) Project (TN202313) and the National Natural Science Foundation of China (Grant Nos. 32272825), the Open Project Program of the International Joint Research Laboratory of the Universities of Jiangsu Province of China for Domestic Animal Germplasm Resources and Genetic Improvement (IJRLD-KF202210) and, Independent Innovation in Jiangsu Province of China (CX (21) 3119); "Qing Lan Project" and the"High-end talent support program" of Yangzhou University, China.

References

  1. Chen Z, Lu Q, Zhang X, et al. Circ007071 Inhibits unsaturated fatty acid synthesis by Interacting with miR-103-5p to enhance PPARγ expression in the dairy goat mammary gland. J Agric Food Chem 2022;70:13719-29. https://doi.org/10.1021/acs.jafc.2c06174
  2. Chen Z, Cao X, Lu Q, et al. circ01592 regulates unsaturated fatty acid metabolism through adsorbing miR-218 in bovine mammary epithelial cells. Food Funct 2021;12:12047-58. https://doi.org/10.1039/d1fo02797b
  3. Wang MQ, Zhou CH, Cong S, et al. Lipopolysaccharide inhibits triglyceride synthesis in dairy cow mammary epithelial cells by upregulating miR-27a-3p, which targets the PPARG gene. J Dairy Sci 2021;104:989-1001. https://doi.org/10.3168/jds.2020-18270
  4. Wilson HE, Stanton DA, Rellick S, Geldenhuys W, Pistilli EE. Breast cancer-associated skeletal muscle mitochondrial dysfunction and lipid accumulation is reversed by PPARG. Am J Physiol Cell Physiol 2021;320:C577-90. https://doi.org/10.1152/ajpcell.00264.2020
  5. Pham DV, Tilija Pun N, Park PH. Autophagy activation and SREBP-1 induction contribute to fatty acid metabolic reprogramming by leptin in breast cancer cells. Mol Oncol 2021;15:657-78. https://doi.org/10.1002/1878-0261.12860
  6. Zhao Q, Lin X, Wang G. Targeting SREBP-1-mediated lipogenesis as potential strategies for cancer. Front Oncol 2022;12:952371. https://doi.org/10.3389/fonc.2022.952371
  7. Peterson DG, Matitashvili EA, Bauman DE. The inhibitory effect of trans-10, cis-12 CLA on lipid synthesis in bovine mammary epithelial cells involves reduced proteolytic activation of the transcription factor SREBP-1. J Nutr 2004;134:2523-7. https://doi.org/10.1093/jn/134.10.2523
  8. Lu Q, Zong W, Zhang M, Chen Z, Yang Z. The overlooked transformation mechanisms of VLCFAs: peroxisomal β-oxidation. Agriculture 2022;12:947. https://doi.org/10.3390/agriculture12070947
  9. Chen GH, Luo Z, Hogstrand C, Wu K, Ling SC. SREBP1, PPARG and AMPK pathways mediated the Cu-induced change in intestinal lipogenesis and lipid transport of yellow catfish Pelteobagrus fulvidraco. Food Chem 2018;269:595-602. https://doi.org/10.1016/j.foodchem.2018.07.048
  10. Mu T, Hu H, Ma Y, Feng X, Zhang J, Gu Y. Regulation of key genes for milk fat synthesis in ruminants. Front Nutr 2021;8:765147. https://doi.org/10.3389/fnut.2021.765147
  11. Zaidi N, Lupien L, Kuemmerle NB, Kinlaw WB, Swinnen JV, Smans K. Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids. Prog Lipid Res 2013;52:585-9. https://doi.org/10.1016/j.plipres.2013.08.005
  12. Bionaz M, Loor JJ. Gene networks driving bovine mammary protein synthesis during the lactation cycle. Bioinform Biol Insights 2011 May 4 [Epub]. https://doi.org/10.4137/BBI.S7003
  13. Chen Z, Chu S, Liang Y, et al. miR-497 regulates fatty acid synthesis via LATS2 in bovine mammary epithelial cells. Food Funct 2020;11:8625-36. https://doi.org/10.1039/d0fo00952k
  14. Sempere LF, Azmi AS, Moore A. microRNA-based diagnostic and therapeutic applications in cancer medicine. Wiley Interdiscip Rev RNA 2021;12:e1662. https://doi.org/10.1002/wrna.1662
  15. Lu Q, Chen Z, Ji D, et al. Progress on the regulation of ruminant milk fat by noncoding RNAs and ceRNAs. Front Genet 2021;12:733925. https://doi.org/10.3389/fgene.2021.733925
  16. Chen Z, Lu Q, Liang Y, et al. Circ11103 interacts with miR-128/PPARGC1A to regulate milk fat metabolism in dairy cows. J Agric Food Chem 2021;69:4490-500. https://doi.org/10.1021/acs.jafc.0c07018
  17. Monoe Y, Jingushi K, Kawase A, et al. Pharmacological inhibition of miR-130 family suppresses bladder tumor growth by targeting various oncogenic pathways via PTPN1. Int J Mol Sci 2021;22:4751. https://doi.org/10.3390/ijms22094751
  18. Zhang HD, Jiang LH, Sun DW, Li J, Ji ZL. The role of miR130a in cancer. Breast Cancer 2017;24:521-7. https://doi.org/10.1007/s12282-017-0776-x
  19. Wei MC, Wang YM, Wang DW. miR-130a-mediated KLF3 can inhibit the growth of lung cancer cells. Cancer Manag Res 2021;13:2995-3004. https://doi.org/10.2147/CMAR.S281203
  20. Egawa H, Jingushi K, Hirono T, et al. The miR-130 family promotes cell migration and invasion in bladder cancer through FAK and Akt phosphorylation by regulating PTEN. Sci Rep 2016;6:20574. https://doi.org/10.1038/srep20574
  21. Nisenblat V, Bossuyt PM, Shaikh R, et al. Blood biomarkers for the non-invasive diagnosis of endometriosis. Cochrane Database Syst Rev 2016;2016:CD012179. https://doi.org/10.1002/14651858.CD012179
  22. Zhou Q, Liu J, Quan J, Liu W, Tan H, Li W. MicroRNAs as potential biomarkers for the diagnosis of glioma: a systematic review and meta-analysis. Cancer Sci 2018;109:2651-9. https://doi.org/10.1111/cas.13714
  23. Kamity R, Sharma S, Hanna N. MicroRNA-mediated control of inflammation and tolerance in pregnancy. Front Immunol 2019;10:718. https://doi.org/10.3389/fimmu.2019.00718
  24. Wang L, Sinnott-Armstrong N, Wagschal A, et al. A microRNA linking human positive selection and metabolic disorders. Cell 2020;183:684-701.E14. https://doi.org/10.1016/j.cell.2020.09.017
  25. Lee YS, Dutta A. MicroRNAs in cancer. Annu Rev Pathol 2009;4:199-227. https://doi.org/10.1146/annurev.pathol.4.110807.092222
  26. Chen Z, Shi H, Sun S, et al. MiR-183 regulates milk fat metabolism via MST1 in goat mammary epithelial cells. Gene 2018;646:12-9. https://doi.org/10.1016/j.gene.2017.12.052
  27. Chen Z, Qiu H, Ma L, et al. miR-30e-5p and miR-15a synergistically regulate fatty acid metabolism in goat mammary epithelial cells via LRP6 and YAP1. Int J Mol Sci 2016;17:1909. https://doi.org/10.3390/ijms17111909
  28. Tang KQ, Wang YN, Zan LS, Yang WC. miR-27a controls triacylglycerol synthesis in bovine mammary epithelial cells by targeting peroxisome proliferator-activated receptor gamma. J Dairy Sci 2017;100:4102-12. https://doi.org/10.3168/jds.2016-12264
  29. Alarcon CR, Lee H, Goodarzi H, Halberg N, Tavazoie SF. N6-methyladenosine marks primary microRNAs for processing. Nature 2015;519:482-5. https://doi.org/10.1038/nature14281
  30. Lu TX, Rothenberg ME. MicroRNA. J Allergy Clin Immunol 2018;141:1202-7. https://doi.org/10.1016/j.jaci.2017.08.034
  31. Ma S, Zhou B, Yang Q, et al. A transcriptional regulatory loop of master regulator transcription factors, PPARG, and fatty acid synthesis promotes esophageal adenocarcinoma. Cancer Res 2021;81:1216-29. https://doi.org/10.1158/0008-5472.CAN-20-0652
  32. Zheng JS, Chen J, Wang L, et al. Replication of a gene-diet interaction at CD36, NOS3 and PPARG in response to Omega-3 fatty acid supplements on blood lipids: a double-blind randomized controlled trial. EBioMedicine 2018;31: 150-6. https://doi.org/10.1016/j.ebiom.2018.04.012
  33. Jing Y, Chen Y, Wang S, et al. Circadian gene PER2 silencing downregulates PPARG and SREBF1 and suppresses lipid synthesis in bovine mammary epithelial cells. Biology 2021;10:1226. https://doi.org/10.3390/biology10121226
  34. Bionaz M, Loor JJ. Gene networks driving bovine milk fat synthesis during the lactation cycle. BMC Genomics 2008;9:366. https://doi.org/10.1186/1471-2164-9-366
  35. Bionaz M, Loor JJ. Identification of reference genes for quantitative real-time PCR in the bovine mammary gland during the lactation cycle. Physiol Genomics 2007;29:312-9. https://doi.org/10.1152/physiolgenomics.00223.2006