Effect of Maternal Obesity and Preconceptional Weight Loss on Male and Female Offspring Metabolism and Olfactory Performance in Mice

Abstract

According to the “developmental origins of health and disease” (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta. We tracked metabolic and olfactory behavioural trajectories of offspring born to control, obese or WL mothers. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD). After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring metabolic phenotypes but had unexpected effects on olfactory performance: a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. Our results confirm the benefits of maternal preconceptional WL for male offspring metabolic health but highlight some possible adverse outcomes on olfactory-based behaviours.

Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects

“…These results suggest that the male offspring of GD rats are more susceptible to disturbances in body weight, when they are exposed to a high maternal blood glucose level during the middle stage of pregnancy. In this regard, sexual differences in the offspring body weight have been reported in relation to maternal obesity and a maternal high-fat diet model [38,39], where it was shown that the body weight of female offspring did not change.…”

Differential Effects of Post-Weaning Diet and Maternal Obesity on Mouse Liver and Brain Metabolomes

“…The animal model, which received the approval (visa 12/062) of the COMETHEA ethical committee (Comité d'éthique pour l'expérimentation animale), registered with the Comité National de Réflexion Ethique sur l'Expérimentation Animale under the n • 45, in accordance with European Union (Directive 2010/63/EU, 22 September 2010) legislation and the National Charter on the Ethics of Animal Experimentation, has been described elsewhere [21,24]. Briefly, as described in Figure 1, half of the C57BL/6J offspring mice born to control (CTRL), obese (OB) or weight-loss (WL) mothers were fed a control (CD: 20% kcal from proteins, 70% from carbohydrates and 10% from fat; #D12450K, Research Diets, New Brunswick, NJ, USA), and half were fed a high-fat diet (HFD: 20% proteins, 20% carbohydrates and 60% fat; #D12492).…”

“…Full details of diet composition are described in [21]. of Animal Experimentation, has been described elsewhere [21,24]. Briefly, as described in Figure 1, half of the C57BL/6J offspring mice born to control (CTRL), obese (OB) or weight-loss (WL) mothers were fed a control (CD: 20% kcal from proteins, 70% from carbohydrates and 10% from fat; #D12450K, Research Diets, New Brunswick, NJ, USA), and half were fed a high-fat diet (HFD: 20% proteins, 20% carbohydrates and 60% fat; #D12492).…”

“…In the long term, periconceptional maternal obesity was associated with a worsening of diet-induced obesity in male offspring challenged with an HFD from weaning to adulthood. Preconceptional weight loss normalized this phenotype, by improving male weight, but was associated with a modification of olfactory performances in the offspring, whatever the post-weaning diet: WL male offspring exhibited a lower peripheral olfactory sensitivity, and motivation to retrieve a hedonic food in WL mice under CD was not enhanced by fasting [21].…”

“…Its morphology and functions are also altered by obesity and/or maternal HFD [15,16], which can modify dietary and hedonic behaviors in adulthood [17][18][19]. Finally, the function of the olfactory system, which participates in the control of food intake, can also be altered by maternal HFD [20,21]. However, the consequences of a preconceptional maternal weight loss on brain metabolism and associated functions of the progeny remain poorly investigated [22,23].…”