Adiponectin agonist treatment in diabetic pregnant rats

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 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 streptozocin (50mg/kg) on day 12 of gestation. GDM+ADI received 50mg/kg/d AdipoRon from day 14 until delivery. Glycaemia and FA profile were determined in mothers and adult offspring (12wo). AdipoRon tended to reduce fasting glucose in diabetic mothers. Diabetic rats presented fetus 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 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 fetal fat accumulation and improved significantly n-6/n-3 PUFA ratio in offspring at adult state.

AdipoAI suppresses osteoclastogenesis by activating AdipoR1/APPL1: An in vivo experimental study in diabetes‐associated peri‐implantitis

“…AdipoRon, the first orally active adiponectin receptor agonist, mimics the antidiabetic actions of adiponectin by activating adiponectin signalling and the AMPK and PPARα pathways (Okada- Iwabu et al, 2013). Gázquez et al (2021) found that in vivo AdipoRon administration reduced glycaemia in pregnant rats with gestational diabetes mellitus and that the impaired glucose response of their offspring was counteracted. In our study, AdipoAI also significantly reduced hyperglycaemia induced by a high-fat diet, which suggests that AdipoAI might successfully function to control blood glucose.…”

The Antiviral Potential of AdipoRon, an Adiponectin Receptor Agonist, Reveals the Ability of Zika Virus to Deregulate Adiponectin Receptor Expression

“…With regard to adiponectin receptor agonists, AdipoRon transfer across the placenta has not been formally verified. However, a study in rats showed that the oral administration of AdipoRon to gestating females with induced diabetes produced positive antioxidant and anti-inflammatory effects and improved the metabolic status in their offspring [ 102 ]. Further pharmaco-toxicological studies of the effects of AdipoRon on the fetus are therefore required.…”

The Role of Adiponectin during Pregnancy and Gestational Diabetes

“…AdipoRon also protected against lipotoxicity in the hearts of db/db mice [ 204 ]. In 2021, a study in pregnant rats showed that AdipoRon reduced hyperglycemia in dams with GDM and improved long-term glucose tolerance in the offspring of pregnant streptozotocin-induced diabetes treated with AdipoRon [ 205 ]. While experiments using AdipoRon in pregnant diabetic rats by Gazquez et al, are an excellent starting point, this model involves β-cell destruction to induce hyperglycemia, which represents a type 1 diabetes model of diabetes in pregnancy [ 206 ].…”