Unexpected Long-Term Protection of Adult Offspring Born to High-Fat Fed Dams against Obesity Induced by a Sucrose-Rich Diet

Abstract

BackgroundMetabolic and endocrine environment during early life is crucial for metabolic imprinting. When dams were fed a high fat diet (HF diet), rat offspring developed hypothalamic leptin resistance with lean phenotype when weaned on a normal diet. Interestingly, when grown on the HF diet, they appeared to be protected against the effects of HF diet as compared to offspring of normally fed dams. The mechanisms involved in the protective effect of maternal HF diet are unclear.Methodology/Principal FindingsWe thus investigated the impact of maternal high fat diet on offspring subjected to normal or high palatable diet (P diet) on metabolic and endocrine parameters. We compared offspring born to dams fed P or HF diet. Offspring born to dams fed control or P diet, when fed P diet exhibited a higher body weight, altered hypothalamic leptin sensitivity and metabolic parameters suggesting that maternal P diet has no protective effect on offspring. Whereas, maternal HF diet reduces body weight gain and circulating triglycerides, and ameliorates corpulence index of offspring, even when subjected to P diet. Interestingly, this protective effect is differently expressed in male and female offspring. Male offspring exhibited higher energy expenditure as mirrored by increased hypothalamic UCP-2 and liver AdipoR1/R2 expression, and a profound change in the arcuate nucleus astrocytic organization. In female offspring, the most striking impact of maternal HF diet is the reduced hypothalamic expression of NPY and POMC.Conclusions/SignificanceHF diet given during gestation and lactation protects, at least partially, offspring from excessive weight gain through several mechanisms depending upon gender including changes in arcuate nucleus astrocytic organization and increased hypothalamic UCP-2 and liver AdipoR1/2 expression in males and reduced hypothalamic expression of NPY and POMC in females. Taken together our results reveal new mechanisms involved in the protective effect of maternal HF diet.

Influence of abnormally high leptin levels during pregnancy on metabolic phenotypes in progeny mice

“…We minimized the impact of the other factors that influence the progeny phenotype, such as genetic background (26), maternal diet (7,17), litter size, and individual maternal body conditions (38) because the dams belonged to the same line and were fed the same standard diet and because only one male and/or one female from the same mother and only from litters of six pups were studied. In addition, the use of this model allowed us to avoid the impact of stress associated with experimental manipulations (surgery, injections) on progeny development.…”

Dietary factors, epigenetic modifications and obesity outcomes: Progresses and perspectives

“…Nevertheless, not all the studies arise to the same conclusion. There are examples in which HFD given during gestation and lactation protects, at least partially, the offspring from excessive weight gain through different hypothalamic mechanisms (Couvreur et al, 2011). So, more studies are needed to elucidate the intrinsic mechanism related with these effects, and complementary studies in humans should be envisaged.…”

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

“…Findings were similar according to maternal treatment, except Western-type maternal diet tended to induce weaker effects on offspring when control diets were matched for energy (White et al, 2009) or micronutrient (Zhang et al, 2013) content. In general, offspring experimental diets were applied at weaning through the end of the study period; based on the small number exceptions (Arentson-Lantz et al, 2014; Brenseke et al, 2015; Couvreur et al, 2011; Khanal et al, 2014; Llopis et al, 2014; Ong and Muhlhausler, 2014; Vido et al, 2014; Wallace et al, 2012), we observed no remarkable patterns with regard to the post-gestational timing of exposure to experimental offspring diets.…”

“…These experimental diets are high in fat, specifically saturated fat (e.g., (Ainge et al, 2011; Fan et al, 2013; Page et al, 2009; Tamashiro et al, 2009; White et al, 2009)) and in some studies, also high in sugar (e.g., (Couvreur et al, 2011; Khanal et al, 2015)). Therefore, our discussion focuses on maternal or offspring “Western diet”, defined as a diet high in saturated fats and/or sugars.…”