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Intrauterine growth restriction increases circulating mitochondrial DNA and Toll-like receptor 9 expression in adult offspring: could aerobic training counteract these adaptations?

Published online by Cambridge University Press:  22 December 2016

V. Oliveira ,
S. D. Silva Junior ,
M. H. C. de Carvalho ,
E. H. Akamine ,
L. C. Michelini  and
M. C. Franco
V. Oliveira
Affiliation:
School of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil
S. D. Silva Junior
Affiliation:
Physiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
M. H. C. de Carvalho
Affiliation:
Pharmacology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
E. H. Akamine
Affiliation:
Pharmacology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
L. C. Michelini
Affiliation:
Physiology Department, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
M. C. Franco*
Affiliation:
School of Medicine, Nephrology Division, Federal University of São Paulo, São Paulo, Brazil Physiology Department, School of Medicine, Federal University of São Paulo, São Paulo, Brazil
*
*Address for correspondence: M. do Carmo Franco, School of Medicine, Division of Nephrology, Federal University of São Paulo, Rua Botucatu, 703-São Paulo, SP 04023-062, Brazil.(Email maria.franco@unifesp.br)
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Abstract

It has been demonstrated that intrauterine growth restriction (IUGR) can program increase cardiometabolic risk. There are also evidences of the correlation between IUGR with low-grade inflammation and, thus can contribute to development of several cardiometabolic comorbidities. Therefore, we investigated the influence of IUGR on circulating mitochondrial DNA (mtDNA)/Toll-like receptor 9 (TLR9) and TNF-α expression in adult offspring. Considering that the aerobic training has anti-inflammatory actions, we also investigated whether aerobic training would improve these inflammatory factors. Pregnant Wistar rats received ad libitum or 50% of ad libitum diet throughout gestation. At 8 weeks of age, male offspring from both groups were randomly assigned to control, trained control, restricted and trained restricted. Aerobic training protocol was performed on a treadmill and after that, we evaluated circulating mtDNA, cardiac protein expression of TLR9, plasma and cardiac TNF-α levels, and left ventricle (LV) mass. We found that IUGR promoted an increase in the circulating mtDNA, TLR9 expression and plasma TNF-α levels. Further, our results revealed that aerobic training can restore mtDNA/TLR9 content and plasma levels of TNF-α among restricted rats. The cardiac TNF-α content and LV mass were not influenced either by IUGR or aerobic training. In conclusion, IUGR can program mtDNA/TLR9 content, which may lead to high levels of TNF-α. However, aerobic training was able to normalize these alterations. These findings evidenced that the association of IUGR and aerobic training seems to exert an important interaction effect regarding pro-inflammatory condition and, aerobic training may be used as a strategy to reduce deleterious adaptations in IUGR offspring.

Keywords

aerobic trainingfetal programmingheartintrauterine growth restriction
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 8 , Issue 2 , April 2017 , pp. 236 - 243
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Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2016 

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