title: Intrauterine growth restriction increases circulating mitochondrial DNA and Toll-like receptor 9 expression in adult offspring: could aerobic training counteract these adaptations?
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.
authors.affiliation: 1School of Medicine,Nephrology Division,Federal University of São Paulo,São Paulo,Brazil.
authors.forename: V
authors.initials: V
authors.lastname: Oliveira
authors.affiliation: 2Physiology Department,Institute of Biomedical Sciences,University of São Paulo,São Paulo,Brazil.
authors.forename: S D
authors.initials: SD
authors.lastname: Silva Junior
authors.affiliation: 3Pharmacology Department,Institute of Biomedical Sciences,University of São Paulo,São Paulo,Brazil.
authors.forename: M H C
authors.initials: MH
authors.lastname: de Carvalho
authors.affiliation: 3Pharmacology Department,Institute of Biomedical Sciences,University of São Paulo,São Paulo,Brazil.
authors.forename: E H
authors.initials: EH
authors.lastname: Akamine
authors.affiliation: 2Physiology Department,Institute of Biomedical Sciences,University of São Paulo,São Paulo,Brazil.
authors.forename: L C
authors.initials: LC
authors.lastname: Michelini
authors.affiliation: 1School of Medicine,Nephrology Division,Federal University of São Paulo,São Paulo,Brazil.
authors.forename: M C
authors.initials: MC
authors.lastname: Franco
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D000831:Animals, Newborn; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control*; D004272:DNA, Mitochondrial / Q000097:blood / Q000235:genetics*; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology*; D008297:Male; D010805:Physical Conditioning, Animal / Q000379:methods*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D004272:DNA, Mitochondrial; D051217:Toll-Like Receptor 9
keywords: aerobic training; fetal programming; heart; intrauterine growth restriction