Endocrine Abstracts

Introduction: The regulation of glucose and lipid metabolism in the brain is essential to ensure overall neurological health and proper functioning. Increased glycolysis and lipogenesis, if not properly regulated, can potentially lead to an imbalance between energy production in the brain. Glucose and lipid metabolic dysregulation contribute to the development and progression of various brain diseases. Besides other factors maternal undernutrition may alter glucose and lipid metabolism which persist after birth and might lead to pathogenesis of neurodegenerative diseases in the offspring.

Aim: The aim of the present study was to examine the effect of maternal perinatal food restriction (MPFR) on offspring and also determined the impact of Glucagon-like peptide-1 receptor (GLP-1R) agonist, liraglutide, on the enzymes involve in glucose and lipid metabolism in brain cortex of both male and female rat pups with maternal food restriction compared to control group.

Methods: Sprague-Dawley pregnant rats (300g) were randomly assigned to 50% food restriction (MPFR) or ad libitum control groups (CT) at day of pregnancy 12. From GD14 to parturition, pregnant MPFR and CT rats were treated with Liraglutide (100 μg/kg/12 hours, sc.) or vehicle (saline). At postnatal day 21 and before weaning, 16 CT and 16 MPFR male pups and 16 CT and 15 MPFR female pups, half of each group from Liraglutide treated mothers, were sacrificed and brain cortex were analysed by RT-PCR.

Results: Maternal food restriction increased mRNA expression of key enzymes involved in carbohydrate and lipid metabolism in brain cortex of female rat pups: Hexokinase-1, Phosphofructokinase-1, Pyruvate Dehydrogenase Kinase4, 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase3, Glucose-6 phosphate dehydrogenase, Pyruvate Kinase M, Lactate dehydrogenase A, Fatty acid synthase, Acetyl-CoA carboxylase alpha, Carnitine palmitoyl transferase1. Liraglutide administration significantly reduced or completely restored the expression levels of all those enzymes. In male pups just Glucose-6 phosphate dehydrogenase expression was completely suppressed and levels of 6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase3 prominently increased in MPFR, and Liraglutide had no effect.

Conclusion: 1. Maternal perinatal food restriction deeply affected the glucose and lipid metabolic activity in brain cortex of female rat pups but not in males by modifying the expression levels of the majority of key enzymes. As a whole MPFR promotes the increase of both glycolysis and lipolysis in the brain cortex just of females. 2. Liraglutide restored the expression of all those key enzymes and minimizes the effects of maternal food restriction and could offer a promising therapeutic approach for the prevention and treatment of brain diseases.