Acetoacetic acid induces oxidative stress to inhibit the assembly of very low density lipoprotein in bovine hepatocytes.
Dairy cows with fatty liver or ketosis exhibit hyperketonemia, oxidative stress, and a low rate of very low density lipoprotein (VLDL) assembly, and there may be a potential link among these characteristics. Therefore, the objective of this study was to determine the effect of acetoacetic acid (AcAc) on the assembly of VLDL in cow hepatocytes. Cultured cow hepatocytes were treated with different concentrations of AcAc with or without N-acetylcysteine (NAC, an antioxidant). AcAc treatment decreased the mRNA expression and activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and significantly increased malondialdehyde (MDA) content, indicative of oxidative stress. Furthermore, AcAc treatment significantly down-regulated the mRNA expression of apolipoprotein B100 (ApoB100), apolipoprotein E (ApoE), and low density lipoprotein receptor (LDLR), which thus decreased VLDL assembly and increased triglyceride (TG) accumulation in these bovine hepatocytes. Importantly, NAC relieved AcAc-induced oxidative stress and increased VLDL assembly. In summary, these results suggest that AcAc-induced oxidative stress affects the assembly of VLDL, which increases TG accumulation in bovine hepatocytes.
Key Laboratory of Zoonosis,Ministry of Education,College of Veterinary Medicine, Jilin University,5333 Xi'an Road,Changchun,130062, Jilin,China.
Xiaoxia
X
Shi
Key Laboratory of Zoonosis,Ministry of Education,College of Veterinary Medicine, Jilin University,5333 Xi'an Road,Changchun,130062, Jilin,China.
Dangdang
D
Li
Key Laboratory of Zoonosis,Ministry of Education,College of Veterinary Medicine, Jilin University,5333 Xi'an Road,Changchun,130062, Jilin,China.
Qinghua
Q
Deng
Key Laboratory of Zoonosis,Ministry of Education,College of Veterinary Medicine, Jilin University,5333 Xi'an Road,Changchun,130062, Jilin,China.
Zhicheng
Z
Peng
Key Laboratory of Zoonosis,Ministry of Education,College of Veterinary Medicine, Jilin University,5333 Xi'an Road,Changchun,130062, Jilin,China.
Chenxu
C
Zhao
Key Laboratory of Zoonosis,Ministry of Education,College of Veterinary Medicine, Jilin University,5333 Xi'an Road,Changchun,130062, Jilin,China.
Xiaobing
X
Li
Key Laboratory of Zoonosis,Ministry of Education,College of Veterinary Medicine, Jilin University,5333 Xi'an Road,Changchun,130062, Jilin,China.
Zhe
Z
Wang
Key Laboratory of Zoonosis,Ministry of Education,College of Veterinary Medicine, Jilin University,5333 Xi'an Road,Changchun,130062, Jilin,China.
Xinwei
X
Li
Key Laboratory of Zoonosis,Ministry of Education,College of Veterinary Medicine, Jilin University,5333 Xi'an Road,Changchun,130062, Jilin,China.
Guowen
G
Liu
D000090:Acetoacetates / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000032:analysis; D002417:Cattle; D002478:Cells, Cultured; D002681:China; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D022781:Hepatocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000096:biosynthesis*; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D014280:Triglycerides / Q000378:metabolism
D000090:Acetoacetates; D000975:Antioxidants; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D014280:Triglycerides; C016635:acetoacetic acid
Bovine hepatocytes; acetoacetic acid; oxidative stress; very low density lipoproteins