Protective Activities of Fibrinogen Like-Protein 1 on Cardiac Function in Obese Insulin-Resistant Rats by Following the STAT3, Akt, and Erk1/2 Phosphorylation

Fibrinogen like-protein 1 (FGL1) has been shown to exhibit cardioprotective properties. However, the effects of the FGL1 on the heart in insulin resistance induced by high-fat-diet and streptozotocin consumption are not well defined. Therefore, we sought to determine the effects of FGL1 in the obese insulin-resistant rats. Structural analysis indicated that FGL1 has a distinct modular architecture comprising a coiled-coil region, N-terminal signal peptide, and C-terminal fibrinogen-like domain. The experimentally resolved structure revealed a compact, β-strand-rich fibrinogen-like fold with defined loop regions and a characteristic globular molecular surface. A total of 80 male rats weighing 220 ± 5 g were acclimatized and included in the study. Diabetes mellitus was induced in 60 rats through a single administration of streptozotocin (STZ; 60 mg/kg), while 20 rats served as healthy controls without STZ treatment. Following STZ administration, blood glucose levels were measured to confirm the successful induction of diabetes. Rats with blood glucose concentrations exceeding 500 mg/dL were considered diabetic and included in subsequent experimental procedures, whereas those not meeting this criterion were excluded. At the end of the treatment, the cardiac function parameters were determined. Also, the ALP, AST, ALT, and GGT concentrations, aortic flow and coronary flow levels, Max dp/dt and Min dp/dt levels, aortic diastolic pressure, aortic systolic pressure and LVDP levels, pSTAT3/STAT3, pAkt/Akt, pErk1/2/Erk1/2, Bax/Tubulin and Bcl-XL/Tubulin ratios were determined in the examined groups. Diabetic rats had increased blood glucose, ALP, AST, ALT, GGT, aortic diastolic pressure, aortic systolic pressure, LVDP, pSTAT3/STAT3, pAkt/Akt, pErk1/2/Erk1/2, Bax/Tubulin and Bcl-XL/Tubulin. FGL1 significantly decreased the above parameters levels. Furthermore, FGL1 restored the cardiac function. We concluded that FGL1 at 80 µg/kg/day exerted cardioprotective effects against cardiac dysfunction in obese insulin-resistant rats.