Melatonin ameliorates endocrine dysfunction and defective sperm integrity associated with high-fat diet-induced obesity in male Wistar rats.

Obesity (OBS) has been established as a link to male hypogonadism with consequent infertility. Previous studies have shown that melatonin (MEL) modulates hypothalamic-pituitary-gonadal function. The present study therefore investigated the hypothesis that MEL supplementation would attenuate spermatogenic and steroidogenic dysfunctions associated with obesity induced by high-fat diet (HFD). Twenty-four adult male Wistar rats (n = 6/group) were used: control group received vehicle (normal saline), obese group received 40% high-fat diet and distilled water, MEL-treated group received MEL (4 mg/kg), and OBS + MEL group received MEL and 40% HFD and the treatment lasted for 12 weeks. HFD caused increased body weight, glucose intolerance, plasma triglyceride and low-density lipoprotein cholesterol/ very low-density lipoprotein cholesterol and malondialdehyde, as well as decreased antioxidant capacity, high-density lipoprotein cholesterol, gonadotrophin-releasing hormone, follicle-stimulating hormone and testosterone and altered sperm parameters. However, all these alterations were attenuated when supplemented with MEL. Taken together, these results indicate that HFD exposure causes endocrine dysfunction and disrupted sperm parameters in obese animals, which are accompanied by lipid peroxidation/defective antioxidant capacity. In addition, the present results suggest that melatonin supplementation restores endocrine function and sperm integrity in obese rat model by suppression of oxidative stress-dependent mechanism.

Oral L-glutamine restores adenosine and glutathione content in the skeletal muscle and adipose tissue of insulin-resistant pregnant rats.

OBJECTIVES: Mishandling of lipid and glycogen has been documented as a feature of metabolic tissues in insulin resistance-related disorders. However, reports exist detailing that L-glutamine (GLN) protects non-adipose tissue against the deleterious effects of metabolic disorders. Therefore, we hypothesized that GLN would protect skeletal muscle and adipose tissue against the deleterious effects of lipid and glycogen mishandlings by increasing adenosine and glutathione levels in pregnant rats exposed to fructose (FRU)-enriched drinks. METHODS: Pregnant Wistar rats weighing 150 to 180 g were randomly assigned to control, GLN, FRU, and FRU + GLN groups (six rats/group). The groups received vehicle (P.o.), glutamine (1 g/kg), FRU (10%; w/v), and FRU + GLN, respectively, for 19 d. RESULTS: Data show that FRU caused insulin resistance with corresponding increased blood glucose, circulating and pancreatic insulin levels, and lipid accumulation and glycogen depletion in skeletal muscle, but glycogen accumulation and a decreased lipid profile in adipose tissue. Adenosine and glutathione content decreased, whereas adenosine deaminase, xanthine oxidase, uric acid, and malondialdehyde concentrations increased in both tissues. In addition, glucose-6-phosphate dehydrogenase activity decreased in skeletal muscle but remained unaltered in adipose tissue. However, supplementation with GLN improved perturbed lipid and glycogen with a corresponding increase in adenosine and glutathione. CONCLUSIONS: The present results collectively indicate that lipid and glycogen mishandlings caused by high gestational FRU intake result in the depletion of adenosine and glutathione in skeletal muscle and adipose tissue. These findings also suggest that L-glutamine protects against skeletal muscle and adipose tissue dysmetabolism by enhancing adenosine and glutathione.

L-glutamine ameliorates adipose-hepatic dysmetabolism in OC-treated female rats.

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. Therefore, we hypothesized that GLUT supplementation would protect against adipose dysfunction and excess hepatic lipid influx and deposition in EPOC-treated animals by suppressing adenosine deaminase/xanthine oxidase (ADA/XO) activity and improving glucose-6-phosphate dehydrogenase (G6PD)-dependent antioxidant defense. Female Wistar rats weighing 150-180 g were allotted into control, GLUT, EPOC and EPOC + GLUT groups (six rats/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. 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 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. Collectively, the present results indicate that EPOC causes metabolically induced obesity which is associated with adipose dysfunction and hepatic metabolic disturbance. The findings also suggest that glutamine confers metabo-protection with corresponding improvement in adipose and hepatic metabolic function by suppression of ADA/XO activity and enhancement of G6PD-dependent antioxidant defense.

l-glutamine supplementation exerts cardio-renal protection in estrogen-progestin oral contraceptive-treated female rats.

Glycogen and lipid disruptions represent a spectrum of metabolic disorders that are crucial risk factors for cardiovascular disease in estrogen-progestin oral contraceptive (COC) users. l-glutamine (GLN) has been shown to exert a modulatory effect in metabolic disorders-related syndromes. We therefore hypothesized that GLN supplementation would protect against myocardial and renal glycogen-lipid mishandling in COC-treated animals by modulation of Glucose-6-phosphate dehydrogenase (G6PD) and xanthine oxidase (XO) activities. Adult female Wistar rats were randomly allotted into control, GLN, COC and COC + GLN groups (six rats per group). The groups received vehicle (distilled water, p.o.), GLN (1 g/kg), COC containing 1.0 µg ethinylestradiol plus 5.0 µg levonorgestrel and COC plus GLN respectively, daily for 8 weeks. Data showed that treatment with COC led to metabolically-induced obesity with correspondent increased visceral and epicardial fat mass. It also led to increased plasma, myocardial and renal triglyceride, free fatty acid, malondialdehyde (MDA), XO activity, uric acid content and decreased glutathione content and G6PD activity. In addition, COC increased myocardial but not renal glycogen content, and increased myocardial and renal glycogen synthase activity, increased plasma and renal lactate production and plasma aspartate transaminase/alanine aminotransferase (AST/ALT) ratio. However, these alterations were attenuated when supplemented with GLN except plasma AST/ALT ratio. Collectively, the present results indicate that estrogen-progestin oral contraceptive causes metabolically-induced obesity that is accompanied by differential myocardial and renal metabolic disturbances. The findings also suggest that irrespective of varying metabolic phenotypes, GLN exerts protection against cardio-renal dysmetabolism by modulation of XO and G6PD activities.

Oral L-glutamine rescues fructose-induced poor fetal outcome by preventing placental triglyceride and uric acid accumulation in Wistar rats.

BACKGROUND: Metabolic adaptation of pregnant mothers is crucial for placental development and fetal growth/survival. However, evidence exists that indiscriminate consumption of fructose-enriched drink (FED) during pregnancy disrupts maternal-fetal metabolic tolerance with attendant adverse fetal outcomes. Glutamine supplementation (GLN) has been shown to exert a modulatory effect in metabolic disorders. Nevertheless, the effects of GLN on FED-induced poor fetal outcome, and in particular the impacts on placental uric acid/lipid accumulation are unknown. The present study was conducted to test the hypothesis that oral GLN improves fetal outcome by attenuating placental lipid accumulation and uric acid synthesis in pregnant rats exposed to FED. MATERIALS AND METHODS: Pregnant Wistar rats (160-180 g) were randomly allotted to control, GLN, FED and FED + GLN groups (6 rats/group). The groups received vehicle by oral gavage, glutamine (1 g/kg) by oral gavage, fructose (10%; w/v) and fructose + glutamine, respectively, through gestation. RESULTS: Data showed that FED during pregnancy caused placental inefficiency, reduced fetal growth, and caused insulin resistance with correspondent increase in fasting blood glucose and plasma insulin. FED also resulted in an increased placental triglyceride, total cholesterol and de novo uric acid synthesis by activating adenosine deaminase and xanthine oxidase activities. Moreover, FED during pregnancy led to increased lipid peroxidation, lactate production with correspondent decreased adenosine and glucose-6-phosphate dehydrogenase-dependent antioxidant defense. These alterations were abrogated by GLN supplementation. CONCLUSION: These findings implicate that high FED intake during pregnancy causes poor fetal outcome via defective placental uric acid/triglyceride-dependent mechanism. The findings also suggest that oral GLN improves fetal outcome by ameliorating placental defects through suppression of uric acid/triglyceride accumulation.

Glutamine confers renoprotection by normalizing lipid and glutathione content in insulin-resistant pregnant rats.

OBJECTIVE: Increasing consumption of fructose is a major contributor to epidemic metabolic syndrome (MS), and the risk of renal disorders and/or injuries remains high among individuals with MS particularly during pregnancy. Glutamine (GLT) has been demonstrated to have a modulatory effect in MS and/or insulin resistance (IR). This study investigated the effect of GLT on renal lipid accumulation and glutathione depletion induced by high fructose-enriched drink (FED) in pregnant rats and also tested the hypothesis that the renoprotective role of GLT is by suppression of adenosine deaminase (ADA)/xanthine oxidase (XO)/uric acid (UA) pathway. METHODS: Pregnant Wistar rats weighing between 160 and 180 g were allotted into Control, GLT, FED and FED + GLT groups (6 rats/group). The groups received distilled water (vehicle, p. o.), 1 g/kg bw GLT (p.o.), 10% Fructose (w/v) and 10% Fructose (w/v) plus 1 g/kg bw GLT (p.o.) respectively, daily for 19 days. RESULTS: Data showed that FED caused IR, increased body weight gain, blood glucose, plasma insulin, creatinine, urea, lipid accumulation, lipid peroxidation, lactate production, aspartate transaminase and alanine aminotransferase, depressed Glucose-6-phosphate dehydrogenase, sodium-potassium-ATPase activities and glutathione. These alterations were accompanied by increased activity of ADA/XO/UA pathway. However, the FED-induced renal injury and its correlates were normalized by GLT supplementation. CONCLUSION: The present results demonstrate that renal lipid accumulation and glutathione depletion-driven renal injury in pregnant rats is accompanied by increased activity of ADA/XO/UA pathway. The findings also suggest that GLT would confer protection against renal injury by protecting against lipid accumulation and glutathionedepletion, at least in part, through suppression of ADA/XO/UA pathway.