title: Non-esterified fatty acids activate the AMP-activated protein kinase signaling pathway to regulate lipid metabolism in bovine hepatocytes.
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.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, 5333 Xi'an Road, Changchun, 130062, Jilin, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Li
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Liancheng
authors.initials: L
authors.lastname: Lei
authors.forename: Juxiong
authors.initials: J
authors.lastname: Liu
authors.forename: Yuan
authors.initials: Y
authors.lastname: Guan
authors.forename: Zhaoxi
authors.initials: Z
authors.lastname: Liu
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.forename: Wentao
authors.initials: W
authors.lastname: Yang
authors.forename: Chenxu
authors.initials: C
authors.lastname: Zhao
authors.forename: Shixin
authors.initials: S
authors.lastname: Fu
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.forename: Guowen
authors.initials: G
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D002417:Cattle; D002478:Cells, Cultured; D005230:Fatty Acids, Nonesterified / Q000737:chemistry / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D047493:PPAR alpha / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C579800:BML-275; D005230:Fatty Acids, Nonesterified; D009687:Nuclear Proteins; D047493:PPAR alpha; D011720:Pyrazoles; D011743:Pyrimidines; D012333:RNA, Messenger; D051780:Sterol Regulatory Element Binding Protein 1; D000123:Acetyltransferases; C055210:aminoglycoside N1-acetyltransferase; D002334:Carnitine O-Palmitoyltransferase; D055372:AMP-Activated Protein Kinases