Long-term effects of maternal magnesium restriction on adiposity and insulin resistance in rat pups.

ABSTRACT

OBJECTIVE: We investigated the long-term effects of maternal/postnatal magnesium (Mg) restriction on adiposity, glucose tolerance, and insulin secretion in the offspring and the probable biochemical mechanisms associated with them. METHODS AND PROCEDURES Female weanling Wistar/NIN (WNIN) rats received a control diet or 70% Mg-restricted (MgR) diet for 9 weeks and mated with control males. A third of the restricted dams were shifted to control diet from parturition. Half of the pups born to the remaining restricted dams were weaned on to control diet, while the other half continued on MgR diet. Various parameters were determined in the offspring at 18 months of age. RESULTS: The percentage of body fat increased, lean body mass (LBM) and fat free mass (FFM) decreased in restricted offspring and were irreversible by rehabilitation. While glucose tolerance and insulin resistance (IR) were comparable among groups, glucose-stimulated insulin secretion and basal glucose uptake by the diaphragm were significantly decreased in restricted offspring and not corrected by rehabilitation. Plasma leptin was lower, and tumor necrosis factor-alpha (TNF-alpha) was higher in restricted offspring, whereas expression of fatty acid synthase (FAS) and fatty acyl transport protein 1 (FATP 1) was higher in liver and adipose tissue. While changes in FAS and FATP 1 were not correctible by rehabilitation, those in leptin and TNF-alpha were corrected by rehabilitation from parturition but not from weaning. Tissue oxidative stress and antioxidant status were comparable among groups. DISCUSSION: Results indicate that maternal and postnatal Mg status is important in the long-term programming of body adiposity and insulin secretion in rat offspring.