The effects of silymarin and atorvastatin on adipokine, hepatokine, myokine profile and certain metabolic parameters in rats fed a high-fat diet

Introduction: The aim of this study is to comprehensively evaluate the effects of silymarin and atorvastatin on the adipokine, hepatokine, and myokine profile, as well as on various biochemical and metabolic parameters, in rats fed a high-fat diet. Materials and Methods: The study was conducted on forty healthy adult male Wistar Albino rats, eight weeks of age, with an average body weight of 327 g. The animals were randomly allocated into five equal groups: C, HFD, HFD+S, HFD+A, and HFD+AS. The HFD groups were subjected to a high-fat diet for eight weeks. The intervention groups received oral silymarin (100 mg/kg/day) and atorvastatin (10 mg/kg/day) during the same period. At the end of the experiment, blood biochemistry parameters (total cholesterol, HDL-C, LDL-C, triglycerides, AST, ALT, etc.), specific protein markers, as well as histological alterations in the liver and gastrocnemius muscle tissues were evaluated. Results: At the end of the experiment, serum METRNL, creatinine, creatine kinase, urea, total cholesterol, LDL cholesterol, triglyceride levels, and body weight showed statistically significant changes. The METRNL levels in the silymarin, atorvastatin, and combination treatment groups were significantly higher compared with the control group (p=0.003). Creatinine levels in the atorvastatin and combination treatment groups were significantly lower than those in the control group (p=0.004). Creatine kinase and urea levels were significantly lower in all HFD-fed groups compared with the control group (p=0.008 and p<0.001, respectively). Total cholesterol levels were significantly lower in the silymarin group compared with the HFD group (p=0.042). LDL cholesterol levels were significantly lower in the silymarin group compared with the control group (p=0.025). Triglyceride levels were significantly higher in all HFD-fed groups compared with the control group (p<0.001). The HFD group exhibited a significantly greater weight gain compared with the other groups, whereas the atorvastatin group showed the lowest proportional weight gain. In the histopathological examination of liver and muscle tissues, the morphological alterations observed in the HFD group (ballooning degeneration, steatosis, inflammation) were markedly reduced, particularly in the group receiving combined treatment. Conclusion: Silymarin has the potential to effectively reduce LDL-C levels and attenuate weight gain. Both silymarin monotherapy and its combination with atorvastatin markedly alleviated HFD-induced hepatic and muscular tissue injury at the histological level. These beneficial effects were partially reflected in the biochemical parameters as well. The findings suggest that combination therapy may exert protective effects against the tissue- and biochemical-level consequences of dyslipidemia; however, pharmacodynamic interactions and optimal dosing strategies warrant further investigation. Keywords: Rat Wistar, High Fat Diet, Silymarin, Atorvastatin, Dyslipidemia, Adipokine, Hepatokine, Myokine,