Mechanisms and metabolic regulation of PPARα activation in Nile tilapia (Oreochromis niloticus)

Although the key metabolic regulatory functions of mammalian peroxisome proliferator-activated receptor alpha (PPAR alpha) have been thoroughly studied, the molecular mechanisms and metabolic regulation of PPAR alpha activation in fish are less known. In the first part of the present study, Nile tilapia (Nt)PPAR alpha was cloned and identified, and high mRNA expression levels were detected in the brain, liver, and heart. NtPPAR alpha was activated by an agonist (fenofibrate) and by fasting and was verified in primary hepatocytes and living fish by decreased phosphorylation of NtPPAR alpha and/or increased NtPPAR alpha mRNA and protein expression. In the second part of the present work, fenofibrate was fed to fish or fish were fasted for 4 weeks to investigate the metabolic regulatory effects of NtPPAR alpha. 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-C-14] palmitate in vivo, hepatic mitochondrial beta-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 NtPPAR alpha activation; 2) dephosphorylation is the basal NtPPAR alpha activation mechanism rather than enhanced mRNA and protein expression; 3) activated NtPPAR alpha has a hypolipidemic effect by increasing activity and the number of hepatic mitochondria; and 4) PPAR alpha activation affects carbohydrate metabolism by altering energy homeostasis among nutrients. (C) 2016 Elsevier B.V. All rights reserved.