Anti- Asprosin: A Potential Protective Role Against the Progression of Diabetic Nephropathy in Type 2 Diabetic Rats

¹ The Department of Physiology, Faculty of Medicine, Zagazig University, Egypt.

² The Zagazig Obesity Management & Research Unit, Faculty of Medicine, Zagazig University, Egypt.

³ College of Medicine, Al maarefa University, Saudi Arabia

^*Corresponding Author

Wesam M. R. Ashour

Medical Physiology Department

Faculty of Medicine

Zagazig University

Egypt

E-mail: wesam_ashour@yahoo.com

Abstract

Background and objective: Diabetic nephropathy (DN) is a common and serious diabetic complication. Asprosin is a protein secreted by white adipose tissue and induces hepatic glucose release. The purpose of this study was designed to evaluate the potential protective effect of asprosin blockage against progression of nephropathy in type II diabetic rats.

Methods: Type II diabetes mellitus was induced by feeding rats on high fat- diet for four weeks followed by injecting them with low dose of streptozotocin (STZ). We randomly divided thirty rats into three different groups: group I (control), group II (non-treated experimentally induced type II diabetic group) and group III (treated type II diabetic group with anti- asprosin antibody). Rats in group III were divided into three equal subgroups. Group (IIIA), (IIIB) and (IIIC): in which rats were given daily intraperitoneal injections of anti- asprosin antibody at doses of 10, 20 and 30 μg / kg body weight respectively for 8 weeks. After the experiments were finished, serum and kidney tissue samples were gathered. In all groups, body weights (BW), thoracic and abdominal circumferences (TC and AC) were measured. Body mass index (BMI) and AC/TC ratio were calculated. After eight weeks duration, rats were euthanized. Serum levels of insulin, glucose, lipid profile, creatinine, urea, C- reactive protien (CRP) and plasminogen activator inhibitor-1 (PAI-1) were measured; homeostasis model assessment of insulin resistance (HOMA-IR) and creatinine clearance (ml/min) were calculated. Protein in urine was estimated. Moreover, the animal was connected to the Power Lab after carotid artery cannulation to record mean arterial blood pressure (MAP). In addition, the changes in the histopathological aspects of the kidney were examined.

Results: Eight weeks after induction of DM, the mean values of final BMI, final AC/TC ratio, serum levels of glucose, HOMA-IR, triglycerides (TG), total cholesterol (TC), LDL-c, urea, creatinine, CRP, PAI-1, proteinuria and MAP were significantly high (P < 0.001). However, the mean values of serum insulin, HDL-c and creatinine clearance were significantly low (P<0.001) in type 2 diabetic rats (group II) when compared to controls. Furthermore, the current findings showed that, the administered anti- asprosin antibody to type 2 diabetic rats (group IIIC), significantly reduced the mean values of final BMI, final AC/TC ratio, serum levels of glucose, HOMA- IR, TG, TC, LDL-cholesterol, urea, creatinine, CRP, PAI-1, MAP and proteinuria (P<0.001, P<0.001, P <0.001, P<0.001, P<0.001, P<0.001, P<0.001, P<0.001, P<0.01, P<0.001, P<0.001, P<0.001 respectively), while, the mean values of serum levels of HDL-c and creatinine clearance were significantly high (P < 0.001) in comparison to those of group II and group IIIA. However, the mean values of serum levels of insulin showed insignificant change when compared with those of group II and group IIIA (P>0.05).

Conclusions: The current study showed that, anti- asprosin may significantly slow the pathophysiological and biochemical progression of DN in high‑fat diet/STZ-induced type 2 diabetic rats indicating that, it may be used as a novel reno-protective agent in cases of obesity and type 2 DM.

Keywords:Diabetes, Nephropathy, Anti- asprosin, Glucose, Creatinine, Rats

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