Current Research in Pharmacology and Drug Discovery (Jan 2025)
Metformin's impact on asprosin and FBN1 expression: Potential mechanisms beyond insulin sensitivity in type 2 diabetes in rats
Abstract
Background: Asprosin, a novel adipokine released under fasting conditions, may play a significant role in the pathophysiology of type 2 diabetes mellitus (T2DM). The objective of this study is to investigate the effects of metformin on serum asprosin levels and FBN1 gene expression in white adipose tissue in male rats. Methods: Thirty-two male Wistar rats were randomly and equally divided into four groups (n = 8): 1. Control Group (CON): Received standard food; 2. Non-Diabetic Metformin Group (CON + MET): Received standard food and were treated with metformin (400 mg/kg/day) for four weeks; 3. Diabetic Group (DM): Induced with T2DM; and 4. Diabetic Metformin Group (DM + MET): Induced with T2DM and treated with metformin (400 mg/kg/day) for four weeks. Finally, serum asprosin levels, lipid profiles, fasting glucose, and insulin concentrations were measured. The expression level of the FBN1 gene in white adipose tissue was quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Results: Serum asprosin levels were significantly higher in the DM group compared to both the CON and CON + MET groups (P < 0.0001). However, serum asprosin levels were significantly lower in the DM + MET group than in the DM group (P = 0.0003). Additionally, the FBN1 gene expression level in white adipose tissue was significantly higher in the DM group compared to the CON group (P = 0.0053), while FBN1 gene expression was significantly lower in the DM + MET group than in the DM group (P < 0.0001). Furthermore, lipid profile, insulin resistance, and fasting blood sugar improved in the CON + MET and DM + MET groups compared to the CON and DM groups, respectively. Discussion: Our findings in diabetic male rats reveal that metformin treatment significantly downregulates FBN1 gene expression and reduces serum asprosin levels, suggesting a potential mechanism for its therapeutic benefits beyond improving insulin sensitivity.
