Obesogenic diet in mice compromises maternal metabolic physiology and lactation ability leading to reductions in neonatal viability

Abstract

Aims: Diets containing high-fat and high sugar (HFHS) lead to overweight/ obesity. Overweight/obesity increases the risk of infertility, and of the pregnant mother and her child for developing metabolic conditions. Overweight/obesity has been recreated in mice, but most studies focus on the effects of chronic, longterm HFHS diet exposure. Here, we exposed mice to HFHS from 3 weeks prior to pregnancy with the aim of determining impacts on fertility, and gestational and neonatal outcomes.Methods: Time-domain NMR scanning was used to assess adiposity, glucose, and insulin tolerance tests were employed to examine metabolic physiology, and morphological and proteomic analyses conducted to assess structure and nutrient levels of maternal organs and placenta.Results: Fertility measures of HFHS dams were largely the same as controls.HFHS dams had increased adiposity pre-pregnancy, however, exhibited exacerbated lipolysis/hyper-mobilization of adipose stores in late pregnancy. While there were no differences in glucose or insulin tolerance, HFHS dams were hyperglycemic and hyperinsulinemic in pregnancy. HFHS dams had fatty livers and altered pancreatic islet morphology. Although fetuses were hyperglycemic and hyperinsulinemic, there was no change in fetal growth in HFHS dams. There were also reductions in placenta formation. Moreover, there was increased offspring loss during lactation, which was related to aberrant mammary gland development and milk protein composition in HFHS dams.Conclusions: These findings are relevant given current dietary habits and the development of maternal and offspring alterations in the absence of an increase in maternal weight and adiposity during pregnancy, which are the current clinical markers to determine risk across gestation.

Hyperglycaemia, pregnancy outcomes and maternal metabolic disease risk during pregnancy and lactation in a lean gestational diabetes mouse model

“…We found that PDM, but not GDM, increased the number of resorptions and resulted in smaller PN2 litter sizes, and associated with pre‐pregnancy blood glucose levels. Similarly, a mouse study using short‐term high fat high/high sugar feeding reported a reduced litter survival throughout lactation in the high fat/high sugar‐fed group (Lean et al., 2022). Consistent with these findings, higher rates of stillbirths were reported in human PDM and GDM (Dudley, 2007; Mackin et al., 2019; Stacey et al., 2019), and associated with HbA1c (Rackham et al., 2009).…”

Placental adaptations supporting fetal growth during normal and adverse gestational environments

“…Placental thickness is also reduced in rats fed high-fat diets (Song et al, 2017) and there are reports of disorganized labyrinthine zone structure in high-fat-fed mice (Zhang et al, 2022), even if fetal development may not always be impaired. Alterations in placental weight and labyrinthine zone morphology with an obesogenic diet can be linked to reduced neonatal viability (Lean et al, 2022).…”

Exercise and energy

“…7 Another societal challenge that exercises physiology-interestingly and successfully-addresses, is the health risks of children exposed to parental inactivity 8 and metabolic disease. 9 Interestingly, it is not always and only the mother who counts, and the potential preventive strategies resulting from these insights are of great value for the early prevention of metabolic disease. 8 Another interesting publication has studied, in detail, the mechanism and energetic costs of rebuilding muscle following immobilization.…”

“…neuromuscular degenerative diseases 6 and type 2 diabetes 7 . Another societal challenge that exercises physiology—interestingly and successfully—addresses, is the health risks of children exposed to parental inactivity 8 and metabolic disease 9 . Interestingly, it is not always and only the mother who counts, and the potential preventive strategies resulting from these insights are of great value for the early prevention of metabolic disease 8 .…”