Metabolic alterations associated with maternal undernutrition during the first half of gestation lead to a diabetogenic state in the rat

Abstract

Background: Although recent studies have investigated the effect of maternal nutrition on metabolic programming of the offspring, the question whether a nutritional insult during early gestation favours an altered metabolic state of the mother that persists during the remainder period of pregnancy, when foetal growth is maximal, remains to be answered.

Methods: To address this issue, we analysed the effect of 40% food restriction during the first 12 days of gestation on glucose tolerance, as well as on liver and adipose tissue metabolism, in Sprague-Dawley pregnant rats.

Results: We found that undernutrition at early gestation blocks pregnancy-associated accumulation of fat, leading to a net breakdown of lipids that may account for an increased delivery of fatty acids and glycerol to the liver. Together with altered expression of hepatic enzymes, this creates a catabolic state, characterized by decreased lipogenesis and increased β-oxidation, which contributes to the ketonemia of underfed mothers. Furthermore, we observed that undernutrition during early pregnancy impairs insulin sensitivity at this stage and, importantly, exacerbates insulin resistance at late gestation, contributing to a diabetogenic state.

Conclusion: Undernutrition during the first half of pregnancy not only alters liver and adipose tissue metabolism, but also exacerbates the maternal insulin resistance at late gestation, which may increase their risk of gestational diabetes.

General significance: Together, these findings highlight the persistent impact of maternal nutrition during early gestation on the metabolism of the mother during late pregnancy.

Keywords: Adipose tissue; Diabetes; Foetal programming; Gestational diabetes; Insulin resistance; Liver; Metabolism; Pregnancy; Programming.