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

Abstract

Nutritional changes during developmental windows are of particular concern in offspring metabolic disease. Questions are emerging concerning the role of maternal weight changes before conception, particularly for weight loss, in the development of diet-related disorders. Understanding the physiological pathways affected by the maternal trajectories in the offspring is therefore essential, but a broad overview is still lacking. We recently reported both metabolic and behavioral negative outcomes in offspring born to obese or weight-loss mothers and fed a control of high-fat diet, suggesting long-term modeling of metabolic pathways needing to be further characterized. Using non-targeted LC–HRMS, we investigated the impact of maternal and post-weaning metabolic status on the adult male offspring’s metabolome in three tissues involved in energy homeostasis: liver, hypothalamus and olfactory bulb. We showed that post-weaning diet interfered with the abundance of several metabolites, including 1,5-anhydroglucitol, saccharopine and β-hydroxybutyrate, differential in the three tissues. Moreover, maternal diet had a unique impact on the abundance of two metabolites in the liver. Particularly, anserine abundance, lowered by maternal obesity, was normalized by a preconceptional weight loss, whatever the post-weaning diet. This study is the first to identify a programming long-term effect of maternal preconception obesity on the offspring metabolome.

Maternal obesity alters offspring liver and skeletal muscle metabolism in early post‐puberty despite maintaining a normal post‐weaning dietary lifestyle

“…Altered galactose metabolism has been associated with disturbances in metabolic disorders of carbohydrates in the liver, and increased cholesterol concentration which predisposes to age‐related diseases such as cardiovascular disease and non‐alcoholic fatty liver disease 30 . A previous mouse study investigating the impact of maternal and post‐weaning metabolic status on the adult male offspring's metabolome showed an alteration of carbohydrate‐related pathways observed in MO offspring similar to our study 31 . However, it is worth mentioning that MO offspring in the rodent study fed high‐fat diets post‐weaning, which differed from our study where MO offspring fed low cholesterol, low‐fat chow diet (healthy control diet) post‐weaning to early puberty.…”

“…30 A previous mouse study investigating the impact of maternal and post-weaning metabolic status on the adult male offspring's metabolome showed an alteration of carbohydrate-related pathways observed in MO offspring similar to our study. 31 However, it is worth mentioning that MO offspring in the rodent study fed high-fat diets post-weaning, which differed from our study where MO offspring fed low cholesterol, low-fat chow diet (healthy control diet) post-weaning to early puberty. This means that there are possible metabolic imprinting effects caused by early maternal poor nutrition which persists irrespective of dietary changes after weaning and beyond, hence predisposing to age-related diseases.…”

High‐Coverage Metabolome Analysis Reveals Significant Diet Effects of Autoclaved and Irradiated Feed on Mouse Fecal and Urine Metabolomics

“…In a study of the impact of maternal and post‐weaning metabolic status on the adult male offspring's metabolome in liver, hypothalamus and olfactory bulb three tissues involved in energy homeostasis, saccharopine, and other two metabolites were found to be affected by the post‐weaning diet in all three tissues, and the abundance of saccharopine was significantly lower in mice fed a high‐fat diet than a control diet. [ 46 ]…”

Epigenetics and Modulations of Early Flavor Experiences: Can Metabolomics Contribute to Prevention during Weaning?

“…It has been widely discussed that weaning is a crucial stage for the children’s health, on which future food choices also depend; however, nutrimetabolomics data regarding this particular period are very scarce. Safi-Stibler et al [ 52 ] suggests a delicate metabolic role for complementary feeding. Indeed, from the comparative metabolomic analysis of a mouse model, greater metabolic repercussions in the offspring emerged following a high fat post-weaning diet (post-natal effect) compared to the effects caused by maternal obesity (pre-natal effect).…”