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

International Journal of Obesity volume 42, pages 618–624 (2018)Cite this article

Subjects

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 ⩾95) and five eutrophic boys (percentile ⩾5/⩽85) (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-γ (PPARγ), PPARγ 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. PPARγ, 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.

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Acknowledgements

This work was supported by CONACyT (SALUD-2009-01-111494). FV is a co-founder and stockholder in Cardero Therapeutics Inc.

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Authors and Affiliations

  1. Unidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría Dr Silvestre Frenk Freund, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Ciudad de Mexico, México

    R Zamora-Mendoza & H Rosas-Vargas

  2. UMAE Hospital General Dr Gaudencio González Garza, Centro Médico Nacional La Raza, IMSS, Ciudad de Mexico, México

    M T Ramos-Cervantes, P Garcia-Zuniga & H Perez-Lorenzana

  3. División Académica de Ciencias Básicas, Unidad Chontalpa, Universidad Juárez Autónoma de Tabasco, Villahermosa, México

    P Mendoza-Lorenzo

  4. Laboratorio de Biología Molecular. Universidad Panamericana, Escuela de Medicina. Augusto Rodin 498, Ciudad de México, 03920, México

    A C Perez-Ortiz & F J Estrada-Mena

  5. Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de Mexico, México

    A Miliar-Garcia, E Lara-Padilla, G Ceballos & I Ramirez-Sanchez

  6. School of Medicine, University of California, San Diego, La Jolla, CA, USA

    A Rodriguez & F Villarreal

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Correspondence to I Ramirez-Sanchez.

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Zamora-Mendoza, R., Rosas-Vargas, H., Ramos-Cervantes, M. et al. Dysregulation of mitochondrial function and biogenesis modulators in adipose tissue of obese children. Int J Obes 42, 618–624 (2018). https://doi.org/10.1038/ijo.2017.274

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