INTRODUCTION

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disorder affecting 10–24% of the global population (1–4) and is strongly associated with obesity, diabetes, and metabolic syndrome (4,7). Approximately 10–20% of patients progress to non-alcoholic steatohepatitis (NASH), leading to fibrosis and excessive extracellular matrix (ECM) deposition (1,8). Fibrillin-1, a structural ECM protein, and its cleavage product Asprosin, derived from white adipose tissue, are implicated in glucose metabolism and fibrotic mechanisms (9–14). Current treatments primarily target components of metabolic syndrome (6,15); however, lifestyle interventions, particularly aerobic exercise, remain central (13,16). Additionally, resveratrol, a natural polyphenol, has shown anti-fibrotic, antioxidant, and anti-inflammatory effects (17–20). Given the strong relationship between NAFLD and adipose tissue dysfunction, the present study aimed to evaluate the effects of eight weeks of aerobic exercise combined with resveratrol supplementation on the expression of Fibrillin-1 and Asprosin in the adipose tissue of NAFLD-induced rats.
METHODS
In this experimental study, 35 eight-week-old male Wistar rats were randomly assigned to two groups: NAFLD (n = 28) and healthy control (CN; n = 7). NAFLD was induced in rats by feeding them a high-fat diet (22% fat, 50% carbohydrate, 24% protein) for six weeks, while controls received a standard diet (12% fat, 57% carbohydrate, 28% protein) (21). The NAFLD group was further divided into four subgroups: NAFLD, exercise (NAFLDT), resveratrol supplementation (NAFLDRSV), and combined exercise-resveratrol (NAFLDTRSV). Exercise involved an eight-week aerobic treadmill program (5 days/week) with gradually increasing speed (15 to 20 m/min) and duration (5 to 60 min) (22). Resveratrol (20 mg/kg) was administered intraperitoneally daily for eight weeks in relevant groups (23).
After 12 hours of fasting and 48 hours after the last exercise session, rats were anesthetized, and visceral adipose tissue was collected for RNA extraction. Real-time PCR was used to evaluate the expression of Fibrillin-1 and Asprosin genes with specifically designed primers. Statistical analysis was performed by one-way ANOVA followed by Tukey’s post hoc test, with significance set at p ≤ 0.05.
RESULTS
Data analysis revealed a significant difference in the expression level of Fibrillin-1 in adipose tissue among the different groups (F = 18.832, p = 0.0001). Tukey post hoc test revealed a significant increase in Fibrillin-1 expression in the NAFLD, NAFLD-Exercise, and NAFLD-Resveratrol groups compared to the control (p = 0.0001 for all). Additionally, a significant decrease was observed in the NAFLD-Exercise (p = 0.037) and NAFLD-Exercise-Resveratrol (p = 0.0001) groups compared to the NAFLD group. Furthermore, the NAFLD-Exercise-Resveratrol group showed a significant reduction compared to both NAFLD-Exercise (p = 0.037) and NAFLD-Resveratrol (p =0.007) groups.
Analysis of Asprosin expression also revealed significant differences between groups (F = 15.751, p = 0.0001). Asprosin expression was significantly higher in NAFLD, NAFLD-Exercise, and NAFLD-Resveratrol groups compared to Control (p = 0.0001, p = 0.001, and p = 0.001, respectively). Moreover, a significant decrease was observed in the NAFLD-Exercise (p = 0.047) and NAFLD-Exercise-Resveratrol (p = 0.0001) groups compared to the NAFLD group. The NAFLD-Exercise-Resveratrol group also had significantly lower Asprosin expression compared to NAFLD-Exercise (p = 0.047) and NAFLD-Resveratrol (p = 0.026) groups.
CONCLUSION
NAFLD increased Fibrillin-1 and Asprosin expression in adipose tissue, while exercise reversed this effect. Resveratrol alone had no significant impact, but its combination with exercise significantly reduced these markers. Further studies, especially in humans, are needed to confirm the mechanisms and clinical relevance.
Ethical Considerations
Compliance with ethical guidelines
This study was derived from a Master's thesis in Exercise Physiology at Islamic Azad University, Qaemshahr Branch, Iran, and has been approved by the Ethics Committee with the code REC.SARI.IAU.IR.1404.154.
Funding
There is no funding support.
Authors' Contributions
The authors contributed equally to the conceptualization and writing of the article. All of the authors approved the content of the manuscript and agreed on all aspects of the work.
Conflict of Interest
The authors declared that there is no conflict of interest.
Acknowledgments
We are grateful to all the individuals who provided scientific consulting for this paper.