Free and dipeptide forms of L-glutamine supplementation attenuate parameters of oxidative stress and nonalcoholic fatty liver disease (NAFLD), and improve glucose metabolism in insulin resistant Ob/Ob mice

Introduction: The availability of the body’s most abundant amino acid, glutamine is compromised in obesity-associated diabetes. This may impair glucose metabolism by increasing hepatic insulin resistance, oxidative stress and the development of nonalcoholic fatty liver disease (NAFLD).Objective: Evaluate the effects of free and dipeptide (DIP, L-alanyl-L-glutamine) forms of L-glutamine on glucose metabolism, biomarkers of oxidative stress and NAFLD in insulin resistant Ob/Ob mice.Methods: C57/BL6 adult male mice were distributed into five groups: WT and Ob/Ob (CTRL) mice receiving water, and Ob/Ob mice supplemented with either DIP or free L-glutamine (GLN). The supplements were offered in a 4% drinking water solution for 40 days prior to euthanasia. Glucose metabolism was evaluated by glucose and insulin tolerance tests (GTT and ITT, respectively) performed at the end of the 40 days of supplementation. After euthanasia plasma glutamine, glucose, insulin and triglycerides (TG) concentrations were analysed. TG, reduced and oxidized glutathione (GSH and GSSG, respectively), TBARS, translocation of NRF-2, and histology were measured in the liver. Statistical differences between groups were determined using One-way ANOVA with post-hoc Tukey HSD.Results: In plasma, GLN and DIP supplements increased glutamine concentration, while fasting TG, glucose and insulin levels reduced compared to the CTRL group (PConclusion: Free and DIP forms of L-glutamine supplementation attenuate parameters of oxidative stress and NAFLD, and improve glucose metabolism in insulin resistant Ob/Ob mice.