Tarlan Varzandi1, Mahammad Amin Abdollahifar2, Seyed Ali Haeri Rohani3, Abbas Piryaei2, Azita Zadeh-Vakili4, Sajad Jeddi5, Asghar Ghasemi6. 1. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. 2. Department of Anatomical Sciences and Biology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Department of Animal Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran. 4. Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 5. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Sajad.jeddi@sbmu.ac.ir. 6. Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: Ghasemi@endocrine.ac.ir.
Abstract
INTRODUCTION: Nitric oxide (NO) deficiency is associated with obesity and type 2 diabetes. Nitrite, a NO donor, is considered as a new therapeutic agent in diabetes. This study aims at determining effects of long-term nitrite administration on browning of white adipose tissue (WAT) in type 2 diabetic rats. METHODS: Male rats were divided into 4 groups: Control, control + nitrite, diabetes, and diabetes + nitrite. Sodium nitrite (50 mg/L in drinking water) was administered for 3 months. Body weight was measured weekly. Fasting serum levels of glucose and nitric oxide metabolites (NOx) were measured monthly. Histological evaluations and measurement of cyclic guanosine monophosphate (cGMP) and NOx levels in adipose tissue were done at the end of the study. RESULTS: Nitrite decreased serum glucose concentration and body weight gain in diabetic rats by 27.6% and 37.9%, respectively. In diabetic rats, nitrite increased NOx and cGMP levels in inguinal WAT by 95.7% and 33.1%, respectively. Numerical density in WAT of nitrite-treated diabetic rats was higher than in diabetic ones (995 ± 83 vs. 2513 ± 256 cell/mm3, P < 0.001); in addition, total surface area (4.84 ± 0.32 vs. 44.26 ± 9.7, mm2, P < 0.001) and volume of inguinal beige adipose tissue (7.2 ± 0.49 vs. 66.4 ± 14.51 mm3, <0.001) were higher in nitrite-treated diabetic rats compared to diabetic ones. CONCLUSIONS: Favorable effects of long-term nitrite administration in obese type 2 diabetic rats is, at least in part, due to browning of WAT and also associated with increased NOx and cGMP level in adipose tissue. These findings may have potential applications for management of diabesity.
INTRODUCTION:Nitric oxide (NO) deficiency is associated with obesity and type 2 diabetes. Nitrite, a NO donor, is considered as a new therapeutic agent in diabetes. This study aims at determining effects of long-term nitrite administration on browning of white adipose tissue (WAT) in type 2 diabeticrats. METHODS: Male rats were divided into 4 groups: Control, control + nitrite, diabetes, and diabetes + nitrite. Sodium nitrite (50 mg/L in drinking water) was administered for 3 months. Body weight was measured weekly. Fasting serum levels of glucose and nitric oxide metabolites (NOx) were measured monthly. Histological evaluations and measurement of cyclic guanosine monophosphate (cGMP) and NOx levels in adipose tissue were done at the end of the study. RESULTS:Nitrite decreased serum glucose concentration and body weight gain in diabeticrats by 27.6% and 37.9%, respectively. In diabeticrats, nitrite increased NOx and cGMP levels in inguinal WAT by 95.7% and 33.1%, respectively. Numerical density in WAT of nitrite-treated diabeticrats was higher than in diabetic ones (995 ± 83 vs. 2513 ± 256 cell/mm3, P < 0.001); in addition, total surface area (4.84 ± 0.32 vs. 44.26 ± 9.7, mm2, P < 0.001) and volume of inguinal beige adipose tissue (7.2 ± 0.49 vs. 66.4 ± 14.51 mm3, <0.001) were higher in nitrite-treated diabeticrats compared to diabetic ones. CONCLUSIONS: Favorable effects of long-term nitrite administration in obese type 2 diabeticrats is, at least in part, due to browning of WAT and also associated with increased NOx and cGMP level in adipose tissue. These findings may have potential applications for management of diabesity.