#4990 OMEGA-3 FATTY ACID ACTIVATES MITOCHONDRIAL BIOGENESIS AND PINK1 DEPENDENT MITOPHAGY IN KIDNEY AND HEART OF ADENINE INDUCED UREMIC RATS

Abstract Background and Aims Mitochondrial homeostasis is controlled by biogenesis, dynamics, and mitophagy. Mitochondrial dysfunction plays a central role in cardiovascular and renal disease and omega-3 fatty acids (FA) are beneficial for cardiovascular disease. We aimed to investigate whether omega-3 FA regulates the expression of mediators of mitochondrial biogenesis, dynamics, and mitophagy in kidney and heart of adenine-induced uremic rats. Method Sprague-Dawley rats were divided into three groups: normal control, adenine control, and omega-3 FA. Uremia was induced by feeding diets containing 0.75% adenine and 2.5% protein for the first 3 weeks. During next 4 weeks, they were received 2.5% protein with or without omega-3 FA (300 mg/kg/day). The renal and cardiac expression of PGC-1α, SIRT1/3, Nrf2, DRP-1, OPA1, Mfn1/2, PINK1, BNIP3 and NIX were examined by western blot analysis. The qPCR was used to determine mitochondrial DNA (mtDNA). Results Compared to normal, serum creatinine and heart weight/body weight in adenine control was increased and improved in omega-3 FA group. Compared with normal, PGC-1α, SIRT1/3 and Nrf2 were down-regulated in kidney and heart of adenine control. PGC-1α expression of kidney and heart was recovered in omega-3 FA group. DRP-1 of kidney was up-regulated but DRP-1 of heart was down-regulated in adenine control. DRP-1 of heart was recovered in omega-3 FA group. PINK1, BNIP3 and NIX were down-regulated in heart of adenine control and recovered in omega-3 FA group. PINK1 was down-regulated but BNIP3 and NIX were up-regulated in kidney of adenine control and those were mitigated in omega-3 FA group. MtDNA was decreased in kidney and heart of adenine control group but mtDNA of heart was recovered in omega-3 FA group. Conclusion DRP-1 related with mitochondrial fission may oppositely work in uremic kidney and heart. Omega-3 FA is beneficial for mitochondrial homeostasis by activating mitochondrial biogenesis and PINK1 dependent mitophagy in kidney and heart of uremic rats.