New Approaches in Educational Management and Health Sciences

New Approaches in Educational Management and Health Sciences

Combined Effects of Aerobic Exercise and Crocin Supplementation on IGF-1 and VEGF-A Growth Factors in High-Fat Diet-Fed Rats

Document Type : Original Article

Authors
Pooya Shokati 1
Forouzan Fattahi Masrour 2
Zahra Sarlak 3
1 Department of Exercise Physiology, CT.C., Islamic Azad University, Tehran, Iran.
2 Department of Exercise Physiology, CT.C., Islamic Azad University, Tehran, Iran
3 Department of Physical Education and Sport Sciences, Khod.C., Islamic Azad University, Khodabandeh, Iran.
10.22034/edus.2026.596364.1136
Abstract
Introduction and Objective: A high-fat diet can affect growth and angiogenic factors by inducing metabolic disturbances. This study aimed to investigate the combined effects of aerobic exercise and crocin supplementation on IGF-1 and VEGF-A levels in high-fat diet-fed rats.
Methods: This experimental laboratory study included 40 female Wistar rats. After one week of acclimatization, the rats were randomly assigned to the study groups. Initially, 32 rats were fed a high-fat diet for 8 weeks, while 8 rats received a normal diet as the control group. Following obesity induction, the high-fat diet-fed animals were divided into four groups: high-fat diet control, high-fat diet + aerobic exercise, high-fat diet + crocin, and high-fat diet + aerobic exercise + crocin. The interventions were performed for 8 weeks. Aerobic exercise was conducted on a treadmill with a gradual increase in exercise intensity and duration. Crocin was administered orally by gavage at a dose of 60 mg/kg body weight, 5 days per week. Serum IGF-1 and VEGF-A levels were assessed using the ELISA method. Data were analyzed using one-way analysis of variance (ANOVA) followed by the Bonferroni post hoc test at a significance level of p ≤ 0.05.
Results: The results showed that the high-fat diet decreased IGF-1 and VEGF-A levels. Aerobic exercise and crocin supplementation separately resulted in a relative improvement in these indices; however, the greatest effect was observed in the group receiving both aerobic exercise and crocin. The combined intervention also significantly increased IGF-1 and VEGF-A levels compared with the high-fat diet group.
Conclusion: It appears that aerobic exercise and crocin supplementation, particularly when combined, can attenuate the adverse effects of a high-fat diet on factors associated with cardiac growth and remodeling. These interventions may contribute to maintaining cardiac health and adaptation through increasing IGF-1 and VEGF-A levels.
Keywords
Aerobic Exercise
Crocin
High-Fat Diet
Cardiac Remodeling
1.             Pai P, D'Mello RS, Brahme OM, Gogineni YV, Shetty MG, Sundara BK. Unlocking cardiac health: exploring the role of class I HDACs in cardiovascular diseases. Mol Cell Biochem. 2025;480(11):5613-5637. doi: 10.1007/s11010-025-05353-5.
2.             Liu Y, Fan Z, Zhai Y, Huang H, Shi R, Wang T. The multifaceted roles of BAF60 subunits in muscle: regulation of differentiation, reprogramming, and metabolic homeostasis. Front Cell Dev Biol. 2025;13:1594423. doi: 10.3389/fcell.2025.1594423.
3.             Akanda MR, Sabuj MSS, Salam SMA, Jahan E. Molecular Interplay of Gene Network Dynamics, Epigenetic Regulation, and Therapeutic Mapping in Cardiovascular Disease. Cardiovasc Drugs Ther. 2026;40(2):711-724. doi: 10.1007/s10557-025-07739-5.
4.             Karakasis P, Theofilis P, Milaras N, Vlachakis PK, Patoulias D, Karamitsos T, et al. Epigenetic Drivers of Atrial Fibrillation: Mechanisms, Biomarkers, and Therapeutic Targets. Int J Mol Sci. 2025;26(11):5253. doi: 10.3390/ijms26115253.
5.             Wang X, Li X, Wang Y, Ren Z, Du X, Gao J,et al. Nkx1.2 deletion decreases fat production in zebrafish. Obesity (Silver Spring). 2024;32(7):1315-1328. doi: 10.1002/oby.24043.
6.             Yang Y, Rivera L, Fang S, Cavalier M, Suris A, Zhou Y, et al. Maternal high-fat diet alters Tet-mediated epigenetic regulation during heart development. iScience. 2024;27(9):110631. doi: 10.1016/j.isci.2024.110631.
7.             Papaioannou I, Dritsoula A, Kang P, Baliga RS, Trinder SL, Cook E, et al. NKX2-5 regulates vessel remodeling in scleroderma-associated pulmonary arterial hypertension. JCI Insight. 2024;9(10):e164191. doi: 10.1172/jci.insight.164191.
8.             Li X, Fan D, Li Y, Yuan J, Sun W, Zhu Q, Qi L, et al. NKX2-5/LHX1 and UHRF1 Establishing a Positive Feedback Regulatory Circuitry Drives Esophageal Squamous Cell Carcinoma through Epigenetic Dysregulation. Adv Sci (Weinh). 2025;12(20):e2413508. doi: 10.1002/advs.202413508.
9.             Zhang H, Chen J, Wang H, Xiang Q, Liu S. Case Report: The nonsense variation of the cardiac transcription factor NKX2-5 has been identified in a Chinese family with nonsyndromic congenital heart disease. Front Genet. 2025;16:1498144. doi: 10.3389/fgene.2025.1498144.
10. Douglas M, O'Loughlin C, Lynch AT, Prialgauskaite R, Adamson AD, Dibb KM, Kimber SJ, Birket MJ. The generation and validation of two NKX2-5 fluorescent reporter human embryonic stem cell lines: UMANe002-A-1 and UMANe002-A-2. Stem Cell Res. 2024;74:103262. doi: 10.1016/j.scr.2023.103262.
11.          Ko T, Nishijo D, Tsuji-Hosokawa A, Tsuchiya I, Nomura S, Zhang B, et al. Correction of the Murine Model of Congenital Heart Disease Associated With the Nkx2-5 Mutation Using Prime Editing. Circ Genom Precis Med. 2025;18(4):e005194. doi: 10.1161/CIRCGEN.124.005194.
12.          Zubaidi AA, Al-Shamsi A. A Novel Missense Heterozygous Mutation in NKX2-5 Gene in a Family with Congenital Septal Defects and Cardiomyopathy: Case Series and Literature Review. J Pediatr Genet. 2024;13(4):308-314. doi: 10.1055/s-0044-1788252.
13.          Song P, Gao Z, Bao Y, Chen L, Huang Y, et al. Wnt/β-catenin signaling pathway in carcinogenesis and cancer therapy. J Hematol Oncol. 2024;17(1):46. doi: 10.1186/s13045-024-01563-4.
14.          Lynch AT, Douglas M, Kimber SJ, Birket MJ. The generation and validation of a dual cardiac HAND1-Tomato NKX2-5-GFP human embryonic stem cell line UMANe002-A-3. Stem Cell Res. 2024;77:103342. doi: 10.1016/j.scr.2024.103342 .
15.          Xue W, Yang L, Chen C, Ashrafizadeh M, Tian Y, Sun R. Wnt/β-catenin-driven EMT regulation in human cancers. Cell Mol Life Sci. 2024;81(1):79. doi: 10.1007/s00018-023-05099-7.
16.          Li JH, Zhou A, Lee CD, Shah SN, Ji JH, Senthilkumar V, et al. MEF2C regulates NK cell effector functions through control of lipid metabolism. Nat Immunol. 2024;25(5):778-789. doi: 10.1038/s41590-024-01811-2 .
17.          Ward C, Sjulson L, Batista-Brito R. The function of Mef2c toward the development of excitatory and inhibitory cortical neurons. Front Cell Neurosci. 2024;18:1465821. doi: 10.3389/fncel.2024.1465821.
18.          Hu X, Wu J, Shi L, Wang F, He K, Tan P, et al. The transcription factor MEF2C restrains microglial overactivation by inhibiting kinase CDK2. Immunity. 2025;58(4):946-960.e10. doi: 10.1016/j.immuni.2025.02.026.
19.          Basu S, Ro EJ, Liu Z, Kim H, Bennett A, Kang S, et al. The Mef2c Gene Dose-Dependently Controls Hippocampal Neurogenesis and the Expression of Autism-Like Behaviors. J Neurosci. 2024;44(5):e1058232023. doi: 10.1523/JNEUROSCI.1058-23.2023.
20.          Yousefian-Jazi A, Kim S, Chu J, Choi SH, Nguyen PTT, Park U, et al. Loss of MEF2C function by enhancer mutation leads to neuronal mitochondria dysfunction and motor deficits in mice. Mol Neurodegener. 2025;20(1):16. doi: 10.1186/s13024-024-00792-y.
21.          Wang D, Qian W, Wu D, Wu Y, Lu K, Zou G. METTL3 promotes microglial inflammation via MEF2C in spinal cord injury. Cell Tissue Res. 2024;395(2):189-197. doi: 10.1007/s00441-023-03855-6.
22.          Gluba-Sagr A, Franczyk B, Rysz-Górzyńska A, Olszewski R, Rysz J. The Role of Selected lncRNAs in Lipid Metabolism and Cardiovascular Disease Risk. Int J Mol Sci. 2024;25(17):9244. doi: 10.3390/ijms25179244.
23.          Iyer P, Asante DM, Vyavahare S, Jin LT, Ahluwalia P, Kolhe R, et al. Transcriptional Signatures of Aerobic Exercise-Induced Muscle Adaptations in Humans. J Funct Morphol Kinesiol. 2025;10(3):281. doi: 10.3390/jfmk10030281.
24.          Li P, Hu Y, Tong L, Bi X. High-intensity training on CREB activation for improving brain health: a narrative review of possible molecular talks. Front Endocrinol (Lausanne). 2025;15:1498495. doi: 10.3389/fendo.2024.1498495.
25.          Zhou Y, Zhang X, Baker JS, Davison GW, Yan X. Redox signaling and skeletal muscle adaptation during aerobic exercise. iScience. 2024;27(5):109643. doi: 10.1016/j.isci.2024.109643.
26.          Nemes R, Koltai E, Taylor AW, Suzuki K, Gyori F, Radak Z. Reactive Oxygen and Nitrogen Species Regulate Key Metabolic, Anabolic, and Catabolic Pathways in Skeletal Muscle. Antioxidants (Basel). 2018;7(7):85. doi: 10.3390/antiox7070085.
New Approaches in Educational Management and Health Sciences
Volume 3, Issue 2
Summer 2026
Summer 2026
Pages 148-162

  • Receive Date 10 May 2026
  • Revise Date 08 August 2026
  • Accept Date 12 September 2026