Sustained kidney biochemical derangement in treated experimental diabetes: a clue to metabolic memory

Author(s)

de Oliveira, Antonio Anax F. ; de Oliveira, Tiago F. ; Bobadilla, Larissa L. ; Garcia, Camila C. M. ; Berra, Carolina Maria ; de Souza-Pinto, Nadja C. ; Medeiros, Marisa H. G. ; Di Mascio, Paolo ; Zatz, Roberto ; Loureiro, Ana Paula de M.

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, JAN 12 2017.
• Web of Science Citations: 6

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-beta expression, reduced PGC-1 alpha 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. (AU)

• FAPESP's process: 12/08617-4 - Variables on glycemic control and pathogenesis of diabetic nephropathy: research on the phenomenon of metabolic memory
• Grantee: Antonio Anáx Falcão de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 13/11747-0 - Oxidative damage and tubular injury markers in an experimental diabetic nephropathy model
• Grantee: Larissa Leticia Bobadilla
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 12/21636-8 - Transformation of human bronchial epithelial cells by benzo[a]pyrene: metabolic redox processes and DNA methylation / demethylation
• Grantee: Tiago Franco de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral