Synergistic Effects of High-Intensity Interval Training and Berberine Hydrochloride Supplementation on Inflammatory and Hypoxia-Related Gene Expression in Obese Middle-Aged Women
Subject Areas : Journal of Animal BiologyZahra Askarpour Kabir 1 , Rambod Khajei 2 * , Mohammad Reza Hossein Abadi 3 , Akbar Safipour Afshar 4
1 - Department of Sports Sciences, Ne.C., Islamic Azad University, Neyshabur, Iran.
2 - Department of Sports Sciences, Ne.C., Islamic Azad University, Neyshabur, Iran
3 - Department of Sports Sciences, Ne.C., Islamic Azad University, Neyshabur, Iran.
4 - Department of Biology, Ne.C., Islamic Azad University, Neyshabur, Iran
Keywords: High-intensity interval training, Berberine hydrochloride, Inflammation, Hypoxia, NF-κB, HIF-1α, Metabolic health,
Abstract :
Obesity in middle-aged women is associated with increased chronic inflammation and tissue hypoxia, playing a crucial role in metabolic disorders and related diseases. This study aimed to investigate the synergistic effects of high-intensity interval training (HIIT) combined with berberine hydrochloride supplementation on the expression of inflammation-related (NF-κB) and hypoxia-related (HIF-1α) genes, and metabolic indicators in obese middle-aged women. In this randomized controlled clinical trial, 40 obese middle-aged women were randomly divided into three groups: HIIT + berberine (n=14), HIIT + placebo (n=13), and control (n=13). The training protocol included three HIIT sessions per week for eight weeks. The HIIT + berberine group received 1000 mg of berberine hydrochloride daily in two divided doses. Venous blood samples were collected at baseline and after 8 weeks to evaluate NF-κB and HIF-1α gene expression using Real-Time PCR. Clinical indices including BMI, body fat percentage, VO2max, fasting glucose, insulin, insulin resistance (HOMA-IR), and C-reactive protein (CRP) were also measured. The results showed that the expression of NF-κB and HIF-1α genes significantly decreased after the 8-week intervention in the HIIT + berberine group compared to the HIIT + placebo and control groups (P<0.05). Additionally, the HIIT + berberine group demonstrated significant improvements in BMI, body fat percentage, VO2max, CRP, and insulin resistance compared to other groups (P<0.05). The findings of this study suggest that high-intensity interval training combined with berberine hydrochloride supplementation has synergistic effects in reducing NF-κB and HIF-1α gene expression and improving metabolic indices in obese middle-aged women. This combined intervention could be recommended as a novel and effective strategy to enhance metabolic health and reduce the risk of obesity-related diseases.
1. Yadav R, Swetanshu, Singh P. The molecular mechanism of obesity: The science behind natural exercise yoga and healthy diets in the treatment of obesity. Curr Probl Cardiol. 2024;49(2):102345.
2. Ruck L, Wiegand S, Kühnen P. Relevance and consequence of chronic inflammation for obesity development. Mol Cell Pediatr. 2023;10(1):16.
3. Grun LK, Maurmann RM, Scholl JN, Fogaça ME, Schmitz CRR, Dias CK, et al. Obesity drives adipose-derived stem cells into a senescent and dysfunctional phenotype associated with P38MAPK/NF-KB axis. Immun Ageing. 2023;20(1):51.
4. Xia M, Yu Z, Wang Y, Liu D, Wang Y, Wu S, et al. Electroacupuncture Combined with Press Needles Alleviates Simple Obesity via VEGF-C/VEGFR-3/PI3K/AKT Signaling Pathway. Obes Facts. 2025:1-16.
5. Simonsen M, Eggertsen C, Pedersen J, Christiansen S, Vestergaard E, Hagstrøm S, et al. Intensity and enjoyment of play-based HIIT in children and adolescents with obesity. Int J Sports Med. 2025;46(3):207-16.
6. Paramita N, Puspasari BC, Arrody R, Kartinah NT, Andraini T, Mardatillah J, et al. Protective Effect of High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) against Vascular Dysfunction in Hyperglycemic Rats. J Nutr Metab. 2022;2022:5631488.
7. Gaweł E, Hall B, Siatkowski S, Grabowska A, Zwierzchowska A. The Combined Effects of High-Intensity Interval Exercise Training and Dietary Supplementation on Reduction of Body Fat in Adults with Overweight and Obesity: A Systematic Review. Nutrients. 2024;16(3).
8. Ahmad AM, Mahmoud AM, Serry ZH, Mohamed MM, Abd Elghaffar HA. Effects of low-versus high-volume high-intensity interval training on glycemic control and quality of life in obese women with type 2 diabetes. A randomized controlled trial. J Exerc Sci Fit. 2023;21(4):395-404.
9. Wang H, Chen S, Tang Y, Nie K, Gao Y, Wang Z, et al. Berberine promotes lacteal junction zippering and ameliorates diet-induced obesity through the RhoA/ROCK signaling pathway. Phytomedicine. 2024;124:155268.
10. Shou JW, Shaw PC. Berberine Reduces Lipid Accumulation in Obesity via Mediating Transcriptional Function of PPARδ. Int J Mol Sci. 2023;24(14).
11. Poudel A, Zhou JY, Mekala N, Welchko R, Rosca MG, Li L. Berberine hydrochloride protects against cytokine-induced inflammation through multiple pathways in undifferentiated C2C12 myoblast cells. Can J Physiol Pharmacol. 2019;97(8):699-707.
12. Nikseresht M, Dabidi Roshan V, Nasiri K. Inflammatory markers and noncoding‐RNAs responses to low and high compressions of HIIT with or without berberine supplementation in middle‐aged men with prediabetes. Physiological Reports. 2024;12(15):e16146.
13. Olean-Oliveira T, Padilha CS, Figueiredo C, Dorneles GP, Marmett B, Peres A, et al. Central obesity is detrimental to anti-inflammatory, phenotype, and exhaustion markers in mononuclear cells - A cross-sectional study. Clin Nutr ESPEN. 2023;58:397-408.
14. Soltani N, Esmaeil N, Marandi SM, Hovsepian V, Momen T, Shahsanai A, et al. Assessment of the effect of short-term combined high-intensity interval training on TLR4, NF-κB and IRF3 expression in young overweight and obese girls. Public Health Genomics. 2020;23(1-2):26-36.
15. Maturana FM, Martus P, Zipfel S, NIE AM. Effectiveness of HIIE versus MICT in improving cardiometabolic risk factors in health and disease: a meta-analysis. Medicine & Science in Sports & Exercise. 2021;53(3):559-73.
16. Wewege M, Van Den Berg R, Ward R, Keech A. The effects of high‐intensity interval training vs. moderate‐intensity continuous training on body composition in overweight and obese adults: a systematic review and meta‐analysis. Obesity reviews. 2017;18(6):635-46.
17. Crowley E, Powell C, Carson BP, W. Davies R. The effect of exercise training intensity on VO2max in healthy adults: an overview of systematic reviews and meta‐analyses. Translational sports medicine. 2022;2022(1):9310710.
18. Khalafi M, Mojtahedi S, Ostovar A, Rosenkranz SK, Korivi M. High‐intensity interval exercise versus moderate‐intensity continuous exercise on postprandial glucose and insulin responses: A systematic review and meta‐analysis. Obesity Reviews. 2022;23(8):e13459.
19. Al-Shajrawi OM, Alwardat S, Alwardat N, Tengku Din TADAA, Hussain Abdulrazak M, Musa I, et al. Exploring the complex relationship between HIF‑1 (rs11549465) and NFκB1 (rs28362491) variations and obesity. World Academy of Sciences Journal. 2024;6(6):71.
20. Zeng Y, Li W, Ma T, Zhang H, Xu J, Liu K. Early Intervention of Baicalin Suppresses Obesity-Induced Adipose Tissue Fibrotic Remodeling through Interfering NF-κB/HIF-1ɑ/GRK2 Signaling Pathway. Phytomedicine Plus. 2025:100815.
21. Chen Y, Zhang S, Ye L, Chen H, Ma P, Wu D. High‐intensity interval training improves hypothalamic inflammation by suppressing HIF‐1α signaling in microglia of male C57BL/6J mice. The FASEB Journal. 2024;38(14):e23770.
22. DiNicolantonio JJ, McCarty MF, Assanga SI, Lujan LL, O'Keefe JH. Ferulic acid and berberine, via Sirt1 and AMPK, may act as cell cleansing promoters of healthy longevity. Open Heart. 2022;9(1):e001801.
23. Amirazodi M, Mehrabi A, Rajizadeh MA, Bejeshk MA, Esmaeilpour K, Daryanoosh F, et al. The effects of combined resveratrol and high intensity interval training on the hippocampus in aged male rats: an investigation into some signaling pathways related to mitochondria. Iranian Journal of Basic Medical Sciences. 2022;25(2):254.
24. Mehrpuya E, Keshavarz S, Banitalebi E, Naghizadeh H, Ramezani J. Effects of Aerobic Exercise Combined with Berberine Chloride Hydrate Supplementation on the Mitochondrial Biogenesis of Cardiac Muscles in Diabetic Male Rats. Zahedan Journal of Research in Medical Sciences. 2023;25(4).
25. Debes WA, Sadaqa M, Németh Z, Aldardour A, Prémusz V, Hock M. Effect of Resistance Exercise on Body Composition and Functional Capacity in Older Women with Sarcopenic Obesity-A Systematic Review with Narrative Synthesis. J Clin Med. 2024;13(2).
26. Janani S, Sedhunivas R. Effectiveness of exercise interventions on muscle mass among older adults with sarcopenic obesity: A scoping review. Aging Med (Milton). 2024;7(1):115-20.