Preventive effects of l-glutamine on gestational fructose-induced cardiac hypertrophy: involvement of pyruvate dehydrogenase kinase-4

Abstract

Gestational fructose exposure has detrimental health consequences on both the maternal and fetus or offspring in the early or later life, contributing to epidemic rise in cardiometabolic syndrome including cardiac events. l-Glutamine has been shown to mitigate cardiac metabolic stress. However, the effect of l-glutamine on cardiac hypertrophy induced by gestational fructose exposure is not known. We therefore hypothesized that l-glutamine would prevent gestational fructose-induced cardiac hypertrophy, possibly by suppression of pyruvate dehydrogenase kinase-4 (PDK-4). Pregnant Wistar rats were allotted into the control, l-glutamine, gestational fructose exposure, and gestational fructose exposure plus l-glutamine groups (6 rats in each group). The groups received distilled water (vehicle, per os), 1 g/kg body weight l-glutamine (per os), 10% fructose (w/v) and 10% fructose (w/v) plus 1 g/kg l-glutamine (per os), respectively, daily for 19 days. Data from this study showed that gestational fructose-enriched drink caused cardiac hypertrophy with correspondent body weight gain, glucose dysregulation, increased cardiac PDK-4, triglyceride, glycogen, lactate, and uric acid production. On the other hand, defective glutathione-dependent antioxidant barrier was also observed in pregnant rats taking fructose-enriched drink. However, the gestational fructose-induced cardiac hypertrophy and its correlates were attenuated by l-glutamine. The present results demonstrate that gestational fructose-enriched drink induces cardiac hypertrophy that is accompanied by increased PDK-4. The findings also suggest that the inhibitory effect of l-glutamine on PDK-4 prevents the development of cardiac hypertrophy, thereby implying that PDK-4 may be a potential novel therapeutic intervention for cardiac hypertrophy especially in pregnancy.