Dysregulation of mitochondrial function and biogenesis modulators in adipose tissue of obese children

R. Zamora-Mendoza, H. Rosas-Vargas, M. T. Ramos-Cervantes, P. Garcia-Zuniga, H. Perez-Lorenzana, P. Mendoza-Lorenzo, A. C. Perez-Ortiz, F. J. Estrada-Mena, A. Miliar-Garcia, E. Lara-Padilla, G. Ceballos, A. Rodriguez, F. Villarreal, I. Ramirez-Sanchez

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44 Scopus citations

Abstract

Background/Objectives:We aimed to evaluate mitochondrial biogenesis (MB), structure, metabolism and dysfunction in abdominal adipose tissue from male pediatric patients with obesity.Subjects/Methods:Samples were collected from five children with obesity (percentile â 3/495) and five eutrophic boys (percentile â 3/45/â 1/285) (8-12 years old) following parental informed consent. We analyzed the expression of key genes involved in MB (sirtuin-1 (SIRT1), peroxisome proliferator-Activated receptor-i 3 (PPARi 3), PPARi 3 coactivator-1α (PGC1α), nuclear respiratory factors 1 and 2 (NRF1, NRF2) and mitochondrial transcription factor A (TFAM) and surrogates for mitochondrial function/structure/metabolism (porin, TOMM20, complex I and V, UCP1, UCP2, SIRT3, SOD2) by western blot. Citrate synthase (CS), complex I (CI) activity, adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA) content and oxidative stress end points were also determined.Results:Most MB proteins were significantly decreased in samples from children with obesity except complex I, V and superoxide dismutase-2 (SOD2). Similarly, CS and CI activity showed a significant reduction, as well as ATP levels and mtDNA content. PPARi 3, PGC1α, complex I and V and SOD2 were hyperacetylated compared with lean samples. Concurrently, in samples from children with obesity, we found decreased SOD2 activity and redox state imbalance highlighted by decreased reduced glutathione/oxidized glutathione (GSH/GSSG) ratio and significant increases in protein carbonylation.Conclusions:Adipose tissue from children with obesity demonstrates a dysregulation of key modulators of MB and organelle structure, and displays hyperacetylation of key proteins and altered expression of upstream regulators of cell metabolism.

Original languageEnglish
Pages (from-to)618-624
Number of pages7
JournalInternational Journal of Obesity
Volume42
Issue number4
DOIs
StatePublished - 1 Apr 2018

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