title: PPARα agonist, fenofibrate, ameliorates age-related renal injury.
abstract: The kidney ages quickly compared with other organs. Expression of senescence markers reflects changes in the energy metabolism in the kidney. Two important issues in aging are mitochondrial dysfunction and oxidative stress. Peroxisome proliferator-activated receptor α (PPARα) is a member of the ligand-activated nuclear receptor superfamily. PPARα plays a major role as a transcription factor that regulates the expression of genes involved in various processes. In this study, 18-month-old male C57BL/6 mice were divided into two groups, the control group (n=7) and the fenofibrate-treated group (n=7) was fed the normal chow plus fenofibrate for 6months. The PPARα agonist, fenofibrate, improved renal function, proteinuria, histological change (glomerulosclerosis and tubular interstitial fibrosis), inflammation, and apoptosis in aging mice. This protective effect against age-related renal injury occurred through the activation of AMPK and SIRT1 signaling. The activation of AMPK and SIRT1 allowed for the concurrent deacetylation and phosphorylation of their target molecules and decreased the kidney's susceptibility to age-related changes. Activation of the AMPK-FOXO3a and AMPK-PGC-1α signaling pathways ameliorated oxidative stress and mitochondrial dysfunction. Our results suggest that activation of PPARα and AMPK-SIRT1 signaling may have protective effects against age-related renal injury. Pharmacological targeting of PPARα and AMPK-SIRT1 signaling molecules may prevent or attenuate age-related pathological changes in the kidney.
authors.affiliation: Division of Nephrology, Department of Internal, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Eun Nim
authors.initials: EN
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Ji Hee
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Division of Nephrology, Department of Internal, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Division of Nephrology, Department of Internal, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Cheol Whee
authors.initials: CW
authors.lastname: Park
authors.affiliation: Division of Nephrology, Department of Internal, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yoon Sik
authors.initials: YS
authors.lastname: Chang
authors.affiliation: Division of Nephrology, Department of Internal, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: sooncb@catholic.ac.kr.
authors.forename: Bum Soon
authors.initials: BS
authors.lastname: Choi
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004734:Energy Metabolism; D011345:Fenofibrate / Q000494:pharmacology*; D000071316:Forkhead Box Protein O3 / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*; D047493:PPAR alpha / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects*; D056564:Sirtuin 1 / Q000378:metabolism
chemical_list: D000071316:Forkhead Box Protein O3; C474033:FoxO3 protein, mouse; D000960:Hypolipidemic Agents; D047493:PPAR alpha; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D011345:Fenofibrate
keywords: AMPK; Aging; Kidney; Oxidative stress; PPAR-α; SIRT1