L-GLUTAMINE IMPROVES ADIPOSE FUNCTION AND AMELIORATES EXCESS HEPATIC LIPID IN ESTROGEN-PROGESTIN ORAL CONTRACEPTIVE-TREATED FEMALE RATS

Abstract

Objective: Adipose dysfunction and inflammation with or without hepatic defects underlie metabolic obesity. Glutamine (GLU) improves glucoregulation and metabolic indices but its effects on adipose function and hepatic lipid deposition in estrogen-progestin oral contraceptive (EPOC) users are unknown. We therefore hypothesized that GLUT supplementation would protect against adipose dysfunction and excess hepatic lipid influx and deposition in animals treated with EPOC by suppressing adenosine deaminase (ADA) activity and improving glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant defense. Design and method: Female Wistar rats weighing between 150–180 g were allotted into control, GLUT, EPOC and EPOC + GLUT groups (six rats per group). The groups received vehicle (distilled water, p.o.), GLUT (1 g/kg), EPOC containing 1.0 μg ethinylestradiol plus 5.0 μg levonorgestrel and EPOC plus GLUT respectively, daily for 8 weeks. Glucoregulatory parameters were determined by homeostatic model of assessment (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI), while metabolically-induced obesity was determined using triglyceride-glucose index. Plasma and tissue biochemical analysis were estimated with enzyme-linked immunosorbent assay kits or fluorescence assay as appropriate Results: Results showed that the administration of EPOC caused glucose dysregulation and increased triglyceride-glucose index and visceral adiposity, but the body weight and liver weight were not affected. However, EPOC significantly decreased adipose lipid, G6PD and glutathione, and increased glycogen synthesis, ADA, XO, uric acid, lipid peroxidation, lactate production and Gamma-glutamyl transferase activity (GGT). On the other hand, EPOC significantly increased hepatic lipid, ADA, XO, uric acid, lipid peroxidation and lactate production, and decreased glycogen synthesis, G6PD and glutathione. Nevertheless, supplementation with glutamine attenuated these alterations. Conclusions: Collectively, the present results indicate that EPOC causes metabolically-induced obesity which is associated with adipose dysfunction and hepatic metabolic defection. The findings also suggest that glutamine confers metabo-protection with corresponding improvement in adipose and hepatic metabolic function by suppression of ADA activity and enhancement of G6PD-dependent antioxidant defense (Figure 1).