In utero exposure to prepregnancy maternal obesity and postweaning high-fat diet impair regulators of mitochondrial dynamics in rat placenta and offspring

被引:61
|
作者
Borengasser, Sarah J. [1 ,2 ]
Faske, Jennifer [1 ]
Kang, Ping [1 ]
Blackburn, Michael L. [1 ]
Badger, Thomas M. [1 ,2 ]
Shankar, Kartik [1 ,2 ]
机构
[1] Arkansas Childrens Nutr Ctr, Little Rock, AR 72202 USA
[2] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA
关键词
mitochondrial dynamics; developmental programming; pregnancy; PGC1; alpha/beta; mitofusin; DNA COPY NUMBER; SKELETAL-MUSCLE; INSULIN-RESISTANCE; BODY-COMPOSITION; ANIMAL-MODELS; UNITED-STATES; ERR-ALPHA; EXPRESSION; PREGNANCY; FUSION;
D O I
10.1152/physiolgenomics.00059.2014
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The proportion of pregnant women who are obese at conception continues to rise. Compelling evidence suggests the intrauterine environment is an important determinant of offspring health. Maternal obesity and unhealthy diets are shown to promote metabolic programming in the offspring. Mitochondria are maternally inherited, and we have previously shown impaired mitochondrial function in rat offspring exposed to maternal obesity in utero. Mitochondrial health is maintained by mitochondrial dynamics, or the processes of fusion and fission, which serve to repair damaged mitochondria, remove irreparable mitochondria, and maintain mitochondrial morphology. An imbalance between fusion and fission has been associated with obesity, insulin resistance, and reproduction complications. In the present study, we examined the influence of maternal obesity and postweaning high-fat diet (HFD) on key regulators of mitochondrial fusion and fission in rat offspring at important developmental milestones which included postnatal day (PND)35 (2 wk HFD) and PND130 (similar to 16 wk HFD). Our results indicate HFD-fed offspring had reduced mRNA expression of presenilin-associated rhomboid-like (PARL), optic atrophy (OPA)1, mitofusin (Mfn)1, Mfn2, fission (Fis)1, and nuclear respiratory factor (Nrf)1 at PND35, while OPA1 and Mfn2 remained decreased at PND130. Putative transcriptional regulators of mitochondrial dynamics were reduced in rat placenta and offspring liver and skeletal muscle [peroxisome proliferator-activated receptor gamma coactivator (PGC1)alpha, PGC1 beta, and estrogen-related receptor (ERR)alpha], consistent with indirect calorimetry findings revealing reduced energy expenditure and impaired fat utilization. Overall, maternal obesity detrimentally alters mitochondrial targets that may contribute to impaired mitochondrial health and increased obesity susceptibility in later life.
引用
收藏
页码:841 / 850
页数:10
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