TY - JOUR
T1 - Dysregulation of mitochondrial function and biogenesis modulators in adipose tissue of obese children
AU - Zamora-Mendoza, R.
AU - Rosas-Vargas, H.
AU - Ramos-Cervantes, M. T.
AU - Garcia-Zuniga, P.
AU - Perez-Lorenzana, H.
AU - Mendoza-Lorenzo, P.
AU - Perez-Ortiz, A. C.
AU - Estrada-Mena, F. J.
AU - Miliar-Garcia, A.
AU - Lara-Padilla, E.
AU - Ceballos, G.
AU - Rodriguez, A.
AU - Villarreal, F.
AU - Ramirez-Sanchez, I.
N1 - Publisher Copyright:
© 2018 Macmillan Publishers Limited.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85047274195&partnerID=8YFLogxK
U2 - 10.1038/ijo.2017.274
DO - 10.1038/ijo.2017.274
M3 - Artículo
C2 - 29158541
SN - 0307-0565
VL - 42
SP - 618
EP - 624
JO - International Journal of Obesity
JF - International Journal of Obesity
IS - 4
ER -
