Evaluation of the relationships of fisetin and atorvastatin with adipokine, hepatokine, myokine profiles and metabolic parameters i̇n rats fed a high-fat diet

The aim of this study was to evaluate the effects of fisetin and atorvastatin administration on metabolic parameters and adipokine (asprosin), hepatokine (fetuin-A) and myokine (meteorine-like protein, GDF-15) profiles in rats fed a high-fat diet (HFD). In addition, the protective potential of these agents on liver and skeletal muscle histology was also investigated. In the study, male Wistar rats were randomly divided into five groups: K, Y, YF, YA and YAF. Y groups were fed a high fat diet for 8 weeks. The intervention groups received fisetin (50 mg/kg/day) and atorvastatin (10 mg/kg/day) by oral gavage for 8 weeks. At the end of the study, blood biochemistry (TG, LDL-C, AST, ALT, glucose, urea, creatinine, etc.), specific protein markers (asprosin, fetuin-A, GDF-15, meteorin-like), histological changes in liver and gastrocnemius muscle tissue were examined. Histopathological examinations revealed significant structural deterioration in the liver and muscle tissues in the HFD-treated groups, whereas these damages were significantly reduced in the combined treatment group. Combined treatment minimised liver steatosis, ballooning, inflammation and fibrosis and reduced inflammation and degeneration in muscle tissue. However, limited effect on LDL-C and TG levels was observed in biochemical data; increase in total cholesterol, decrease in glucose level, improvement in creatinine and urea levels were found. No significant differences were observed between the groups in adipokine, hepatokine and myokine levels. The combination of fisetin and atorvastatin significantly decreased NDE-induced liver and muscle tissue damage at histological level. However, these favourable effects were not fully reflected on biochemical parameters. The findings suggest that combination therapy may be protective at the tissue level; however, the effects on metabolic regulation may be limited depending on dose and duration. Therefore, pharmacodynamic interactions and optimum dosing should be investigated in more detail. Keywords: Rat Model, High Fat Diet, Fisetin, Atorvastatin, Adipokine, Hepatokine, Myokine, Liver Histology, Muscle Tissue