miR-497 Regulates LATS1 through the PPARG Pathway to Participate in Fatty Acid Synthesis in Bovine Mammary Epithelial Cells

Genes (Basel). 2023 Jun 5;14(6):1224. doi: 10.3390/genes14061224.

Abstract

Nutrient metabolism is required to maintain energy balance in animal organisms, and fatty acids play an irreplaceable role in fat metabolism. In this study, microRNA sequencing was performed on mammary gland tissues collected from cows during early, peak, and late lactation to determine miRNA expression profiles. Differentially expressed miRNA (miR-497) was selected for functional studies of fatty acid substitution. Simulants of miR-497 impaired fat metabolism [triacylglycerol (TAG) and cholesterol], whereas knockdown of miR-497 promoted fat metabolism in bovine mammary epithelial cells (BMECs) in vitro. In addition, in vitro experiments on BMECs showed that miR-497 could down-regulate C16:1, C17:1, C18:1, and C20:1 as well as long-chain polyunsaturated fats. Thus, these data expand the discovery of a critical role for miR-497 in mediating adipocyte differentiation. Through bioinformatics analysis and further validation, we identified large tumor suppressor kinase 1 (LATS1) as a target of miR-497. siRNA-LATS1 increased concentrations of fatty acids, TAG, and cholesterol in cells, indicating an active role of LATS1 in milk fat metabolism. In summary, miR-497/LATS1 can regulate the biological processes associated with TAG, cholesterol, and unsaturated fatty acid synthesis in cells, providing an experimental basis for further elucidating the mechanistic regulation of lipid metabolism in BMECs.

Keywords: LATS1; bovine mammary epithelial cells; miR-497; milk fat metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cholesterol / genetics
  • Cholesterol / metabolism
  • Epithelial Cells / metabolism
  • Fatty Acids / genetics
  • Fatty Acids / metabolism
  • Female
  • Gene Expression Regulation
  • Mammary Glands, Animal / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • PPAR gamma* / genetics
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Triglycerides / metabolism

Substances

  • PPAR gamma
  • MicroRNAs
  • Fatty Acids
  • Triglycerides
  • Cholesterol
  • Protein Serine-Threonine Kinases

Grants and funding

This research was supported by the National Natural Science Foundation of China (Grant No. 3187130529), the National Natural Science Foundation of China (32002263), the by Jiangsu Modern Dairy Industry Technology System (JATS (2019) 446), the Seed Industry Vitalization Program of Jiangsu Province (JBGS [2021]117) and the Young Elite Scientists Sponsorship Program by CAST (2022QNRC001).