Adiponectin agonist treatment in diabetic pregnant rats.

Antonio Gázquez,Elvira Larqué,Francisca Rodríguez,María D Albaladejo-Otón,María Sánchez-Campillo,Marino B Arnao,Pedro Saura-Garre,Lidia E Martínez-Gascón

doi:10.1530/joe-20-0617

Abstract

Gestational diabetes mellitus (GDM) reduces maternal adiponectin and docosahexaenoic acid (DHA) materno-fetal transfer, which may have negative consequences for the offspring. Our aim was to evaluate the effects of the administration of a novel adiponectin agonist (AdipoRon) to GDM rats on the long-term consequences in glycaemia and fatty acids (FA) profile in the offspring. Pregnant rats were randomized to three groups: GDM rats (GDM, n = 8), GDM rats treated with AdipoRon (GDM + ADI, n = 9), and control rats (n = 10). Diabetes was induced with streptozotocin (50 mg/kg) on day 12 of gestation. GDM+ADI received 50 mg/kg/day AdipoRon from day 14 until delivery. Glycaemia and FA profile were determined in mothers and adult offspring (12 weeks old). AdipoRon tended to reduce fasting glucose in diabetic mothers. Diabetic rats presented the foetus with intrauterine growth restriction and higher adiposity, which tried to be counteracted by AdipoRon. In the adult offspring, both GDM + ADI and control animals showed better glucose recovery after oral glucose overload with respect to GDM. DHA in offspring plasma was significantly reduced in both GDM and GDM + ADI compared to controls (P = 0.043). Nevertheless, n-6/n-3 polyunsaturated FA (PUFA) ratio improved in plasma of GDM + ADI adult offspring (GDM: 14.83 ± 0.85a%; GDM + ADI: 11.49 ± 0.58b%; control: 10.03 ± 1.22b%, P = 0.034). Inflammatory markers and oxidative stress were reduced in the adult offspring of AdipoRon-treated mothers. In conclusion, AdipoRon administration to pregnant diabetic rats improved glycaemia in the mothers and long-term glucose tolerance in the offspring. In addition, it tended to reduce excessive foetal fat accumulation and improved n-6/n-3 PUFA ratio significantly in offspring at the adult state.

Highlights

Gestational diabetes mellitus (GDM) prevalence is increasing in women due to the obesity epidemic; the ideal management of GDM remains controversial (Mack & Tomich 2017)
Female rats were mated (1:1), and the first day of gestation was estimated by the presence of a mating plug in the cage. They were randomly assigned to three groups of 15 animals each: diabetic rats (GDM), diabetic rats treated with adiponectin agonist (AdipoRon, Biorbyt, UK) (GDM + ADI), and healthy controls without diabetes
Adiponectin agonist (AdipoRon) administration tended to reduce glycaemia in diabetestreated mothers compared to non-treated dams (Fig. 1A), following HbAlc the same non-significant trend (P = 0.073 GDM vs GDM + ADI)

Summary

Introduction

Gestational diabetes mellitus (GDM) prevalence is increasing in women due to the obesity epidemic; the ideal management of GDM remains controversial (Mack & Tomich 2017). It is estimated that one out of six live births is affected by hyperglycaemia in pregnancy, most of those due to GDM GDM is associated with neonatal adverse outcomes such as large for gestational age infants and increased risk of obesity and cardiometabolic disease later in life (Boney et al 2005, Lawlor et al 2010), contributing to the perpetuation of the vicious cycle of obesity, diabetes, and metabolic syndrome. There is growing evidence of the GDM long-term consequences for mothers, who have a higher risk of developing type 2 diabetes and cardiovascular disease (Bellamy et al 2009, Kramer et al 2019)

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