PPARα activation enhances the ability of nile tilapia (Oreochromis niloticus) to resist Aeromonas hydrophila infection

Peroxisome proliferator-activated receptor alpha (PPAR alpha) plays critical physiological roles in energy metabolism, antioxidation and immunity of mammals, however, these functions have not been fully understood in fish. In the present study, Nile tilapia (Oreochromis niloticus) were fed with fenofibrate, an agonist of PPAR alpha, for six weeks, and subsequently challenged with Aeromonas hydrophila. The results showed that PPAR alpha was efficiently activated by fenofibrate through increasing mRNA and protein expressions and protein dephosphorylation. PPAR alpha activation increased significantly mitochondrial fatty acid beta-oxidation efficiency, the copy number of mitochondrial DNA and expression of monoamine oxidase (MAO), a marker gene of mitochondria. Meanwhile, PPAR alpha activation also increased significantly the expression of NADH dehydrogenase [ubiquinone] 1 alpha sub-complex subunit 9 (NDUFA9, complex I) and mitochondrial cytochrome c oxidase 1 (MTCO1, complex IV). The fenofibrate-fed fish had higher survival rate when exposed to A. hydrophila. Moreover, the fenofibrate-fed fish also had higher activities of immune and antioxidative enzymes, and gene expressions of anti-inflammatory cytokines, while had lower expressions of pro-inflammatory cytokine genes. Taken together, PPAR alpha activation improved the ability of Nile tilapia to resist A. hydrophila, mainly through enhancing mitochondrial fatty acids beta-oxidation, immune and antioxidant capacities, as well as inhibiting inflammation. This is the first study showing the regulatory effects of PPAR alpha activation on immune functions through increasing mitochondria-mediated energy supply in fish.