Mechanisms and metabolic regulation of PPARα activation in Nile tilapia (Oreochromis niloticus).
Although the key metabolic regulatory functions of mammalian peroxisome proliferator-activated receptor α (PPARα) have been thoroughly studied, the molecular mechanisms and metabolic regulation of PPARα activation in fish are less known. In the first part of the present study, Nile tilapia (Nt)PPARα was cloned and identified, and high mRNA expression levels were detected in the brain, liver, and heart. NtPPARα was activated by an agonist (fenofibrate) and by fasting and was verified in primary hepatocytes and living fish by decreased phosphorylation of NtPPARα and/or increased NtPPARα mRNA and protein expression. In the second part of the present work, fenofibrate was fed to fish or fish were fasted for 4weeks to investigate the metabolic regulatory effects of NtPPARα. A transcriptomic study was also performed. The results indicated that fenofibrate decreased hepatic triglyceride and 18C-series fatty acid contents but increased the catabolic rate of intraperitoneally injected [1-(14)C] palmitate in vivo, hepatic mitochondrial β-oxidation efficiency, the quantity of cytochrome b DNA, and carnitine palmitoyltransferase-1a mRNA expression. Fenofibrate also increased serum glucose, insulin, and lactate concentrations. Fasting had stronger hypolipidemic and gene regulatory effects than those of fenofibrate. Taken together, we conclude that: 1) liver is one of the main target tissues of the metabolic regulation of NtPPARα activation; 2) dephosphorylation is the basal NtPPARα activation mechanism rather than enhanced mRNA and protein expression; 3) activated NtPPARα has a hypolipidemic effect by increasing activity and the number of hepatic mitochondria; and 4) PPARα activation affects carbohydrate metabolism by altering energy homeostasis among nutrients.
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China.
Li-Jun
LJ
Ning
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China.
An-Yuan
AY
He
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China.
Jia-Min
JM
Li
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China.
Dong-Liang
DL
Lu
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China.
Jian-Gang
JG
Jiao
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China.
Ling-Yu
LY
Li
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China.
Dong-Liang
DL
Li
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China.
Mei-Ling
ML
Zhang
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China.
Li-Qiao
LQ
Chen
Laboratory of Aquaculture Nutrition and Environmental Health (LANEH), School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: zydu@bio.ecnu.edu.cn.
Zhen-Yu
ZY
Du
D000818:Animals; D005227:Fatty Acids / Q000378:metabolism; D005786:Gene Expression Regulation; D022781:Hepatocytes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D047493:PPAR alpha / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D017210:Tilapia / Q000235:genetics*; D014280:Triglycerides / Q000378:metabolism
D005227:Fatty Acids; D047493:PPAR alpha; D012333:RNA, Messenger; D014280:Triglycerides
Dephosphorylation; Fasting; Fenofibrate; Metabolism; Nile tilapia; PPARα activation