Effect of long-term nitrite administration on browning of white adipose tissue in type 2 diabetic rats: A stereological study.

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.