Exercise performed during pregnancy positively modulates liver metabolism and promotes mitochondrial biogenesis of female offspring in a rat model of diet-induced gestational diabetes

Abstract

Gestational diabetes mellitus (GDM) is associated with a high-risk for metabolic complications in offspring. However, exercise is recognized as a non-pharmacological strategy against metabolic disorders and is recommended in GDM treatment. This study aimed to investigate whether gestational exercise (GE) could modulate maternal high-fat high-sucrose (HFHS) diet-related hepatic metabolic and mitochondrial outcomes in female offspring of mothers with HFHS-induced GDM. Female Sprague-Dawley rats were fed with control or HFHS diet and kept sedentary or submitted to GE. Their female offspring were fed with control diet and kept sedentary. Hepatic lipid accumulation, lipid metabolism regulators, mitochondrial biogenesis and dynamics markers, and microRNAs associated to the regulation of these markers were evaluated. Female offspring of GDM mothers showed increased body weight at early age, whereas GE prevented this effect of maternal HFHS-feeding and reduced hepatic lipid accumulation. GE stimulated hepatic mRNA transcription and protein expression of mitochondrial biogenesis markers (peroxisome proliferator-activated receptor-gamma co-activator-1alpha and mitochondrial transcription factor A) and mRNA transcription of mitochondrial dynamics markers (mitofusin-1, mitofusin-2, and dynamin-related protein-1) that were altered by maternal GDM, while mitochondrial dynamics markers protein expression was not affected by maternal diet/GE except for optic atrophy-1. MicroRNAs associated with these processes (miR-122, miR-34a, miR-130b, miR-494), and the expression of auto/mitophagy- and apoptosis-related proteins were not substantially influenced by altered intrauterine environment. Our findings suggest that GE is an important regulator of the intrauterine environment positively affecting liver metabolism and promoting liver mitochondrial biogenesis in female offspring despite eventual effects of maternal HFHS-feeding and related GDM.

Keywords: Fetal programming; Gestational exercise; Physical exercise; Pregnancy.