Post-weaning diet determines metabolic risk in mice exposed to overnutrition in early life

Abstract

BackgroundMaternal overnutrition during pregnancy is associated with an increased risk of obesity and cardiometabolic disease in the offspring; a phenomenon attributed to ‘developmental programming’. The post-weaning development of obesity may associate with exacerbation of the programmed metabolic phenotype. In mice, we have previously shown that exposure to maternal overnutrition causes increased weight gain in offspring before weaning, but exerts no persistent effects on weight or glucose tolerance in adulthood. In order to determine whether post-weaning exposure to a cafeteria diet might lead to an exacerbation of programmed effects, offspring born and raised by mothers on control (CON) or cafeteria (DIO) diets were transferred onto either CON or DIO diets at weaning.FindingsPost-weaning DIO caused the development of obesity, with hyperglycaemia and hyperinsulinaemia in males; and obesity with hyperinsulinaemia in females and with increased cholesterol levels in both sexes. Exposure to maternal overnutrition during pregnancy and lactation caused only subtle additional effects on offspring phenotype.ConclusionsThese results suggest that post-weaning exposure to a high-fat high-sugar diet has a more profound effect on offspring weight gain and glucose tolerance than exposure to maternal overnutrition. These data emphasise the importance of optimising early life nutrition in offspring of both obese and lean mothers.

Life-long Maternal Cafeteria Diet Promotes Tissue-Specific Morphological Changes in Male Offspring Adult Rats

“…Surprisingly, adult F1 offspring, derived from dams exposed to life-long CAF diet, including during pregnancy and lactation periods, did not present alterations in body weight, adipose tissue content, and parameter plasmatic evaluated. Our results are in agreement with those of other reports that have used an almost identical experimental design, and did not observe significant modifications in offspring (Akyol et al 2012, Mucellini et al 2014), or only a marginal effect in the exacerbation of the obesity phenotype, in adult F1 offspring (King et al 2014). However, our findings contrast with data from other studies showing that offspring derived Degree III…”

“…In addition, the programmed metabolic phenotype, found in the offspring, could be exacerbated during growth, in particular when offspring are also exposed to a life-long obesogenic diet (Mucellini et al 2014). However, while the effects of maternal over nutrition on weight gain and metabolism in offspring, before weaning, are well characterized (Smith andRyckman 2015, Sedaghat et al 2015), their persistent effects on adipose tissue content, glucose tolerance, insulin resistance and liver abnormalities in adulthood are contradictory (Tamashiro et al 2009, Akyol et al 2012, King et al 2014, Mucellini et al 2014. Thus, understanding how pre-and post-natal environment interactions affect the growth and development of offspring is fundamental, since the timing of an insult determines which organ or systems will be altered, when obesity occurs and the severity of diseases, later in life (Lukaszewski et al 2013, Lee 2015, Ramírez-Lopes et al 2015.…”

“…Moreover, post-weaning exposure to hypercaloric diet induces the development of obesity, disruption in glucose-insulin homeostasis, dyslipidemia, liver steatosis, and cardiovascular diseases (King et al 2014, Mucellini et al 2014. As such, experimental obesity can be produced by maternal or post-weaning dietary manipulations.…”

Developmental Programming: Priming Disease Susceptibility for Subsequent Generations

“…The effects of postnatal diet among offspring exposed to prenatal Western-style diet, compared to offspring of control-fed dams, varied within study by gender [42, 45, 46]. In other studies, the effects of postnatal overnutrition were similar across prenatal diet groups [53, 54] or, for body weight outcomes, even weaker [55, 56]. In many studies, it was difficult to distinguish between cumulative versus synergistic effects of prenatal and postnatal diets, as investigation of “priming” or “hyper-responsivity” to postnatal exposures was not the primary aim of the research.…”

From fatalism to mitigation: A conceptual framework for mitigating fetal programming of chronic disease by maternal obesity

“…In other cases, effects of post-weaning diet were more severe than the effects of maternal diet (Akyol et al, 2012; King et al, 2014), or the adverse effects of maternal obesity were observed regardless of post-weaning diet (Bayol et al, 2010; Thorn et al, 2014). In six studies, maternal high fat diet protected against the adverse effects of a postnatal Western-type diet with regard to weight gain (Couvreur et al, 2011; Ferezou-Viala et al, 2007; Howie et al, 2009; Mucellini et al, 2014), insulin sensitivity (Ferezou-Viala et al, 2007; Mucellini et al, 2014), lipid levels (Shankar et al, 2008), or blood pressure (Elahi et al, 2009).…”