title: Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory.
abstract: The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA. The sustained decrease of uric acid clearance in treated diabetes may support the prolonged kidney biochemical alterations observed after tight glycemic control, and this regulation is likely mediated by the sustained decrease of AMPK activity and the induction of inflammation. This manuscript proposes the first consideration of the possible role of hyperuricemia and the underlying biochemical changes as part of metabolic memory in diabetic nephropathy development after glycemic control.
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 580, Bloco 13 B, CEP 05508-000, São Paulo, Brazil.
authors.forename: Antonio Anax F
authors.initials: AA
authors.lastname: de Oliveira
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 580, Bloco 13 B, CEP 05508-000, São Paulo, Brazil.
authors.forename: Tiago F
authors.initials: TF
authors.lastname: de Oliveira
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 580, Bloco 13 B, CEP 05508-000, São Paulo, Brazil.
authors.forename: Larissa L
authors.initials: LL
authors.lastname: Bobadilla
authors.affiliation: Center for Research in Biological Sciences &Department of Biological Sciences, Institute of Physical and Biological Sciences, Federal University of Ouro Preto, Campus Morro do Cruzeiro, Ouro Preto, MG, Brazil.
authors.forename: Camila C M
authors.initials: CC
authors.lastname: Garcia
authors.affiliation: Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, CEP 05508-000, São Paulo, Brazil.
authors.forename: Carolina Maria
authors.initials: CM
authors.lastname: Berra
authors.affiliation: Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, CEP 05508-000, São Paulo, Brazil.
authors.forename: Nadja C
authors.initials: NC
authors.lastname: de Souza-Pinto
authors.affiliation: Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, CEP 05508-000, São Paulo, Brazil.
authors.forename: Marisa H G
authors.initials: MH
authors.lastname: Medeiros
authors.affiliation: Department of Biochemistry, Institute of Chemistry, University of São Paulo, Av. Prof. Lineu Prestes 748, CEP 05508-000, São Paulo, Brazil.
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Mascio
authors.affiliation: Nephrology Division, Department of Internal Medicine, School of Medicine, University of São Paulo, Av. Dr. Arnaldo, 455, 3-s/3342, CEP 01246-903, São Paulo, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Zatz
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of São Paulo, Av. Prof. Lineu Prestes 580, Bloco 13 B, CEP 05508-000, São Paulo, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: de M Loureiro
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D005215:Fasting / Q000097:blood; D005650:Fumarates / Q000378:metabolism; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology; D007668:Kidney / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D008954:Models, Biological; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000378:metabolism; D010766:Phosphorylation; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004272:DNA, Mitochondrial; D005650:Fumarates; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016212:Transforming Growth Factor beta; D008315:Malondialdehyde; D000263:Adenylate Kinase