Cell Biochemistry and Biophysics

, Volume 67, Issue 3, pp 1157–1169 | Cite as

Non-Esterified Fatty Acids Activate the AMP-Activated Protein Kinase Signaling Pathway to Regulate Lipid Metabolism in Bovine Hepatocytes

  • Xinwei Li
  • Xiaobing Li
  • Hui Chen
  • Liancheng Lei
  • Juxiong Liu
  • Yuan Guan
  • Zhaoxi Liu
  • Liang Zhang
  • Wentao Yang
  • Chenxu Zhao
  • Shixin Fu
  • Peng Li
  • Guowen Liu
  • Zhe Wang
Original Paper

Abstract

Non-esterified fatty acids (NEFAs) act as signaling molecules involved in regulating genes expression to modulate lipid metabolism. However, the regulation mechanism of NEFAs on lipid metabolism in dairy cows is unclear. 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 NEFAs and AMPKα inhibitors (BML-275). NEFAs increased AMPKα phosphorylation through up-regulating the protein levels of liver kinase B1. Activated AMPKα increased the expression and transcriptional activity of peroxisome proliferator-activated receptor α (PPARα). NEFAs also directly activate the PPARα independent of AMPKα. Activated PPARα increased the lipolytic genes expression to increase lipid oxidation. Furthermore, activated AMPKα inhibited the expression and transcriptional activity of the sterol regulatory element-binding protein 1c and carbohydrate responsive element-binding protein, which reduced the expression of lipogenic genes, thereby decreasing lipid synthesis. Activated AMPKα phosphorylated and inhibited acetyl-CoA carboxylase and increased carnitine palmitoyltransferase-1 activity, which increased lipid oxidation. Consequently, the triglyceride content in the NEFAs-treated hepatocytes was significantly decreased. These results indicate that NEFAs activate the AMPKα signaling pathway to increase lipid oxidation and decrease lipid synthesis in hepatocytes, which in turn, generates more ATP to relieve the negative energy balance in transition dairy cows.

Keywords

Non-esterified fatty acids AMP-activated protein kinase signaling pathway Lipid oxidation Lipid synthesis 

Abbreviations

NEB

Negative energy balance

NEFAs

Non-esterified fatty acids

AMPK

AMP-activated protein kinase

LKB1

Liver kinase B1

PPARα

Peroxisome proliferator-activated receptor α

SREBP-1c

Sterol regulatory element-binding protein 1c

ChREBP

Carbohydrate responsive element-binding protein

TG

Triglyceride

ACO

Acyl-CoA oxidase

CPT1

Carnitine palmitoyltransferase 1

CPT2

Carnitine palmitoyltransferase 2

L-FABP

Liver fatty acid-binding protein

ACSL

Acyl-CoA synthetase long-chain

ACC1

Acetyl-CoA carboxylase 1

p-ACC1

Phosphorylated-ACC1

FAS

Fatty acid synthase

SCD-1

Stearoyl-CoA desaturase-1

p-AMPKα

Phosphorylated-AMPKα

EMSA

Electrophoretic mobility shift assay

PUFAs

Polyunsaturated fatty acids

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Xinwei Li
    • 1
  • Xiaobing Li
    • 1
  • Hui Chen
    • 1
  • Liancheng Lei
    • 1
  • Juxiong Liu
    • 1
  • Yuan Guan
    • 1
  • Zhaoxi Liu
    • 1
  • Liang Zhang
    • 1
  • Wentao Yang
    • 1
  • Chenxu Zhao
    • 1
  • Shixin Fu
    • 2
  • Peng Li
    • 3
  • Guowen Liu
    • 1
  • Zhe Wang
    • 1
  1. 1.Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary MedicineJilin UniversityChangchunChina
  2. 2.Institute of Animal Science and TechnologyHeilongjiang Bayi Agriculture UniversityDaqingChina
  3. 3.College of Animal Science and Veterinary MedicineShenyang Agricultural UniversityShenyangChina

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