Interaction between Maternal and Offspring Diet to Impair Vascular Function and Oxidative Balance in High Fat Fed Male Mice

Abstract

AimsTo determine the impact of maternal and post-weaning consumption of a high fat diet on endothelium-dependent vasorelaxation and redox regulation in adult male mouse offspring.MethodsFemale C57BL6J mice were fed an obesogenic high fat diet (HF, 45% kcal fat) or standard chow (C, 21% kcal fat) pre-conception and throughout pregnancy and lactation. Post-weaning, male offspring were continued on the same diet as their mothers or placed on the alternative diet to give 4 dietary groups (C/C, HF/C, C/HF and HF/HF) which were studied at 15 or 30 weeks of age.ResultsThere were significant effects of maternal diet on offspring body weight (p<0.004), systolic blood pressure (p = 0.026) and endothelium-dependent relaxation to ACh (p = 0.004) and NO production (p = 0.005) measured in the femoral artery. With control for maternal diet there was also an effect of offspring post-weaning dietary fat to increase systolic blood pressure (p<0.0001) and reduce endothelium-dependent relaxation (p = 0.022) and ACh-mediated NO production (p = 0.007). There was also a significant impact of age (p<0.005). Redox balance was perturbed, with altered regulation of vascular enzymes involved in ROS/NO signalling.ConclusionsMaternal consumption of a HF diet is associated with changes in vascular function and oxidative balance in the offspring of similar magnitude to those seen with consumption of a high fat diet post-weaning. Further, this disadvantageous vascular phenotype is exacerbated by age to influence the risk of developing obesity, raised blood pressure and endothelial dysfunction in adult life.

Developmental programming by maternal obesity in 2015: Outcomes, mechanisms, and potential interventions

“…Given that obesity itself increases the risk of heart disease, cardiac dysfunction may be exaggerated in high-fat-fed offspring exposed to maternal obesity. Indeed, the combination of maternal HFD and post-weaning exposure to HFD culminates in reduced vasorelaxation in both mice and nonhuman primates (Fan et al, 2013;Torrens et al, 2012), with increased oxidative stress in the femoral arteries of adult male offspring (Torrens et al, 2012).…”

“…As well as increased adiposity, ectopic lipid deposition has also been observed in the liver and pancreas of offspring exposed to maternal obesity Oben et al, 2010a,b), in association with altered hepatic mRNA and protein expression profiles indicative of increased lipogenesis (Bruce et al, 2009), elevated markers of oxidative damage Bringhenti et al, 2014;Torrens et al, 2012), inflammation, fibrosis and increased sympathetic nervous system activation (Oben et al, 2010a). These results provide evidence for an increased risk of non-alcoholic fatty liver and pancreas diseases (NAFLD and NAFPD, respectively) in offspring of obese mothers, a pathology which commonly occurs in obesity when the normal capacity of white adipose tissue for lipid storage has been exceeded.…”

“…Animal studies have confirmed that maternal obesity programs metabolic syndrome-like outcomes in the offspring including impaired insulin action and glucose homeostasis (Martin-Gronert et al, 2010;Samuelsson et al, 2008;Shankar et al, 2010;Shelley et al, 2009), hypertension, and cardiovascular dysfunction Fernandez-Twinn et al, 2012;Samuelsson et al, 2008), as well as increased adiposity (Bayol et al, 2008;Samuelsson et al, 2008;Song et al, 2015), and an increased susceptibility to diet-induced obesity (DIO) (Bayol et al, 2007;Howie et al, 2009;Kirk et al, 2009;Nivoit et al, 2009;Samuelsson et al, 2008;Shankar et al, 2008;Torrens et al, 2012). The choice of animal model is often a compromise between practicality of the research and translatability to humans.…”

Developmental aspects of a life course approach to healthy ageing

“…; Torrens et al . ). In humans, increased levels of reactive oxygen species in the placenta may be linked to neonatal insulin resistance and obesity in response to maternal obesity or gestational diabetes (Coughlan et al .…”

Effect of maternal canthaxanthin and 25‐hydroxycholecalciferol supplementation on the performance of ducklings under two different vitamin regimens

“…Dietary regimen of offspring has been reported to influence their response to maternal nutritional status (Torrens et al., ; Cheong et al., ). In Gao's study (Gao et al., ), maternal xanthophylls supplementation increased antioxidant status of progeny chicks, regardless of the xanthophylls content of chicks' diet.…”