title: Essential amino acid ratios and mTOR affect lipogenic gene networks and miRNA expression in bovine mammary epithelial cells.
abstract: BACKGROUND
  The objective of this study was to study how changing the ratio of Lys to Thr, Lys to His, and Lys to Val affects the expression of lipogenic genes and microRNA (miRNA) in bovine mammary epithelial cells.
  
  
  RESULTS
  Triplicate cultures with the respective "optimal" amino acid (AA) ratio (OPAA = Lys:Met 2.9:1; Thr:Phe 1.05:1; Lys:Thr 1.8:1; Lys:His 2.38:1; Lys:Val 1.23:1) plus rapamycin (OPAARMC; positive control), OPAA, Lys:Thr 2.1:1 (LT2.1), Lys:Thr 1.3:1 (LT1.3), Lys:His 3.05:1 (LH3.0), or Lys:Val 1.62:1 (LV1.6) were incubated in lactogenic medium for 12 h. The expression of 15 lipogenic genes and 7 miRNA were evaluated. Responses to LT2.1, LT1.3, LH3.0, and LV1.6 relative to the control (OPAARMC) included up-regulated expression of ACSS2, FABP3, ACACA, FASN, SCD, LPIN1, INSIG1, SREBF1, PPARD, and NR1H3 (commonly known as LXR-α). Furthermore, LV1.6 up-regulated expression of ACSL1, DGAT1, and RXRA and down-regulated PPARG expression. Although no effect of OPAA on expression of PPARG was observed, compared with the control, OPAA up-regulated expression of the PPAR targets ACSS2, FABP3, ACACA, FASN, SCD, LPIN1, INSIG1, and SREBF1. Compared with the control, the expression of the anti-lipogenic MIR27AB was down-regulated by OPAA, LT2.1, LT1.3 and LH3.0. In contrast, compared with the control, the expression of the pro-lipogenic MIR21 was up-regulated by LT2.1, LT1.3, LH3.0, and LV1.6.
  
  
  CONCLUSIONS
  The observed up-regulation of lipogenic gene networks and the changes in expression of key miRNA involved in the control of lipogenic balance are indicative of a potentially important role of EAA ratios and mTOR signaling in the regulation of milk fat synthesis.
authors: Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou, 310058 People's Republic of China.
authors: Shanshan
authors: S
authors: Li
authors: Department of Animal Sciences, Mammalian NutriPhysioGenomics, University of Illinois, 1207 West Gregory Drive, Urbana, IL 61801 USA.
authors: Afshin
authors: A
authors: Hosseini
authors: Department of Animal Science, University of Lavras, Lavras, MG 37200-000 Brazil.
authors: Marina
authors: M
authors: Danes
authors: NUPEEC, Departamento de Clínicas Veterinária, Programa de Pós-Graduação em Biotecnologia, Universidade Federal de Pelotas, 96010-900 Pelotas, RS Brazil.
authors: Carolina
authors: C
authors: Jacometo
authors: Institute of Dairy Science, College of Animal Sciences, Zhejiang University, Yuhangtang Road 866, Hangzhou, 310058 People's Republic of China.
authors: Jianxin
authors: J
authors: Liu
authors: Department of Animal Sciences, Mammalian NutriPhysioGenomics, University of Illinois, 1207 West Gregory Drive, Urbana, IL 61801 USA.
authors: Juan J
authors: JJ
authors: Loor
keywords: Amino acids; Milk fat synthesis; Nutrigenomics; mTOR