Maternal Metformin Treatment during Gestation and Lactation Improves Skeletal Muscle Development in Offspring of Rat Dams Fed High-Fat Diet

Abstract

Maternal high-fat (HF) diet is associated with offspring metabolic disorder. This study intended to determine whether maternal metformin (MT) administration during gestation and lactation prevents the effect of maternal HF diet on offspring’s skeletal muscle (SM) development and metabolism. Pregnant Sprague-Dawley rats were divided into four groups according to maternal diet {CHOW (11.8% fat) or HF (60% fat)} and MT administration {control (CT) or MT (300 mg/kg/day)} during gestation and lactation: CH-CT, CH-MT, HF-CT, HF-MT. All offspring were weaned on CHOW diet. SM was collected at weaning and 18 weeks in offspring. Maternal metformin reduced plasma insulin, leptin, triglyceride and cholesterol levels in male and female offspring. Maternal metformin increased MyoD expression but decreased Ppargc1a, Drp1 and Mfn2 expression in SM of adult male and female offspring. Decreased MRF4 expression in SM, muscle dysfunction and mitochondrial vacuolization were observed in weaned HF-CT males, while maternal metformin normalized them. Maternal metformin increased AMPK phosphorylation and decreased 4E-BP1 phosphorylation in SM of male and female offspring. Our data demonstrate that maternal metformin during gestation and lactation can potentially overcome the negative effects of perinatal exposure to HF diet in offspring, by altering their myogenesis, mitochondrial biogenesis and dynamics through AMPK/mTOR pathways in SM.

Maternal High-Fat Diet Reduces Type-2 Neural Stem Cells and Promotes Premature Neuronal Differentiation during Early Postnatal Development

“…A maternal HFD animal model was constructed following standard procedure ( Figure 1 A). Our previous work showed that maternal HFD intake during pregnancy and lactation affects the metabolic phenotype of dams, including higher intake energy, increased adiposity, and higher plasma leptin and insulin concentrations [ 26 , 29 ]. In the current study, we focused on the effects of a maternal HFD on offspring brain development.…”

Developmental metformin exposure does not rescue physiological impairments derived from early exposure to altered maternal metabolic state in offspring mice

“…Although not statistically significant, metformin seems to counteract the maternal HFD-induced increase in insulin levels in male offspring. Previous studies have also shown that maternal metformin exposure reduces plasma insulin levels in the offspring of obese dams at weaning [ 89 ]. Furthermore, we observed an effect of early metformin exposure on reducing ghrelin levels in both P16 males and females.…”

The Role of Gut Microbiota in Gestational Diabetes Mellitus Affecting Intergenerational Glucose Metabolism: Possible Mechanisms and Interventions

“…During pregnancy, MT increases brain weight as well as total thoracic and abdominal visceral weight in intrauterine growth restriction (IUGR)-affected, small-for-gestational-age (SGA) offspring [72]. Maternal MT treatment during pregnancy and lactation ameliorates the negative effects of a maternal HFD on offspring, and the underlying mechanism may be that MT improves skeletal muscle development through the AMPK/mTOR pathway [73]. In addition, there are sex differences in MT treatment, with females having a smaller body size and males having lower relative weights of major internal organs [74].…”