miR-34a-5p Increases Hepatic Triglycerides and Total Cholesterol Levels by Regulating ACSL1 Protein Expression in Laying Hens

Int J Mol Sci. 2019 Sep 8;20(18):4420. doi: 10.3390/ijms20184420.

Abstract

Accumulating evidence has shown that miR-34a serves as a posttranscriptional regulatory molecule of lipid metabolism in mammals. However, little studies about miR-34a on lipid metabolism in poultry have been reported until now. To gain insight into the biological functions and action mechanisms of miR-34a on hepatic lipid metabolism in poultry, we firstly investigated the expression pattern of miR-34a-5p, a member of miR-34a family, in liver of chicken, and determined its function in hepatocyte lipid metabolism by miR-34a-5p overexpression and inhibition, respectively. We then validated the interaction between miR-34a-5p and its target using dual-luciferase reporter assay, and explored the action mechanism of miR-34a-5p on its target by qPCR and Western blotting. Additionally, we looked into the function of the target gene on hepatocyte lipid metabolism by gain- and loss-of-function experiments. Our results indicated that miR-34a-5p showed a significantly higher expression level in livers in peak-laying hens than that in pre-laying hens. miR-34a-5p could increase the intracellular levels of triglycerides and total cholesterol in hepatocyte. Furthermore, miR-34a-5p functioned by inhibiting the translation of its target gene, long-chain acyl-CoA synthetase 1 (ACSL1), which negatively regulates hepatocyte lipid content. In conclusion, miR-34a-5p could increase intracellular lipid content by reducing the protein level, without influencing mRNA stability of the ACSL1 gene in chickens.

Keywords: ACSL1; chicken; liver; miR-34a-5p; total cholesterol; triglycerides.

MeSH terms

  • Animals
  • Base Sequence
  • Cell Line
  • Chickens / genetics*
  • Chickens / metabolism*
  • Cholesterol / metabolism*
  • Coenzyme A Ligases / genetics*
  • Coenzyme A Ligases / metabolism
  • Gene Expression
  • Lipid Metabolism
  • Liver / metabolism*
  • MicroRNAs / chemistry
  • MicroRNAs / genetics*
  • Triglycerides / metabolism*

Substances

  • MicroRNAs
  • Triglycerides
  • Cholesterol
  • Coenzyme A Ligases