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

Abstract

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 (∼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)α, PGC1β, and estrogen-related receptor (ERR)α], 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.

When two obese parents are worse than one! Impacts on embryo and fetal development

“…Either maternal or paternal HFD in isolation has been shown to change the transcriptome of the developing placenta (5,8,46,75). Thus, we determined whether there were additive effects of combined paternal and maternal HFD on placental gene expression during gestation.…”

“…As both in vivo-and in vitro-derived fetuses and placentas were reduced in size with combined paternal and maternal obesity, and since both pater-nal and maternity obesity alone alter placental gene expression (5,8,46,75), we established whether key imprinting, growth, nutrition, and mitochondrial specific gene regulation were further impaired when both parents were obese. We observed sex-specific effects on placental gene expression that were expected given the numerous reports of sex-specific phenotypes in offspring in models of maternal and paternal obesity (18,19,22,23,63,66,67).…”

Mitochondrial activity and dynamics changes regarding metabolism in ageing and obesity

“…In fact, it has been shown that, in both, rodents and humans, skeletal muscle from high-fat fed conditions show higher H 2 O 2 -mitochondrial production affecting the redox state of the cells but without changes in the mitochondrial respiratory function (Anderson et al, 2009). Further experiments performed in rats demonstrated that exposure to prepregnancy maternal obesity impairs the activity of factors involved in mitochondrial dynamics in the offspring (Borengasser et al, 2014).…”

Antibiotics-Induced Obesity: A Mitochondrial Perspective

“…Recent animal-based studies have suggested the effect of maternal obesity and postweaning high-fat diet on the key regulators of mitochondrial fusion and fission. Maternal obesity detrimentally changes mitochondrial targets which in turn, contribute to mitochondrial dysfunction and increased risk of obesity [24]. Potential modifications in mitochondrial bioenergetics may arise due to specific mutations that occur in the mitochondrial DNA.…”