Acetic acid activates the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes

PLoS One. 2013 Jul 4;8(7):e67880. doi: 10.1371/journal.pone.0067880. Print 2013.

Abstract

The effect of acetic acid on hepatic lipid metabolism in ruminants differs significantly from that in monogastric animals. Therefore, the aim of this study was to investigate the regulation mechanism of acetic acid on the hepatic lipid metabolism in dairy cows. The AMP-activated protein kinase (AMPK) signaling pathway plays a key role in regulating hepatic lipid metabolism. In vitro, bovine hepatocytes were cultured and treated with different concentrations of sodium acetate (neutralized acetic acid) and BML-275 (an AMPKα inhibitor). Acetic acid consumed a large amount of ATP, resulting in an increase in AMPKα phosphorylation. The increase in AMPKα phosphorylation increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α, which upregulated the expression of lipid oxidation genes, thereby increasing lipid oxidation in bovine hepatocytes. Furthermore, elevated AMPKα phosphorylation reduced the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and the carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid biosynthesis in bovine hepatocytes. In addition, activated AMPKα inhibited the activity of acetyl-CoA carboxylase. Consequently, the triglyceride content in the acetate-treated hepatocytes was significantly decreased. These results indicate that acetic acid activates the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in bovine hepatocytes, thereby reducing liver fat accumulation in dairy cows.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / genetics*
  • AMP-Activated Protein Kinases / metabolism
  • Acetyl-CoA Carboxylase / antagonists & inhibitors
  • Acetyl-CoA Carboxylase / genetics
  • Acetyl-CoA Carboxylase / metabolism
  • Animals
  • Cattle
  • Cells, Cultured
  • Female
  • Gene Expression Regulation
  • Hepatocytes / cytology
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Lipid Metabolism / drug effects*
  • Lipogenesis / drug effects*
  • Liver / cytology
  • Liver / drug effects*
  • Liver / metabolism
  • PPAR alpha / agonists
  • PPAR alpha / genetics
  • PPAR alpha / metabolism
  • Phosphorylation
  • Pyrazoles / pharmacology
  • Pyrimidines / pharmacology
  • Signal Transduction / drug effects*
  • Sodium Acetate / pharmacology*
  • Sterol Regulatory Element Binding Protein 1 / antagonists & inhibitors
  • Sterol Regulatory Element Binding Protein 1 / genetics
  • Sterol Regulatory Element Binding Protein 1 / metabolism
  • Triglycerides / metabolism

Substances

  • BML-275
  • PPAR alpha
  • Pyrazoles
  • Pyrimidines
  • Sterol Regulatory Element Binding Protein 1
  • Triglycerides
  • Sodium Acetate
  • AMP-Activated Protein Kinases
  • Acetyl-CoA Carboxylase

Grant support

This study was supported by the National Key Basic Research Program of China (No. 2011CB100800), the Program for New Century Excellent Talents in University (NCET-11-0199), the National Key Technology R&D Program (Grant No. 2012BAD12B03), the National Natural Science Foundation of China (Beijing, China) (Grant Nos. 30871897, 31072178, 31172372, 31272621) and the Science Fund for Distinguished Young Scholars of Jilin University (Grant No. 201100009). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.