Journal of Exercise Physiology in Special Populations

The effect of high-intensity interval training and ginger supplementation on AMPK/SREBP-1c/ACC pathway markers in male rats with nonalcoholic fatty liver disease.

Document Type : Original Article

Authors

1 PhD candidate in Exercise Physiology, Department of Physical Education and Sport Sciences, Boj.C., Islamic Azad University, Bojnourd, Iran.

2 Assistant Professo at Department of Physical Education and Sport Sciences, Boj.C., Islamic Azad University, Bojnourd, Iran

3 Associate Professor at Department of Physical Education and Sport Sciences, Boj.C., Islamic Azad University, Bojnourd, Iran.

4 bojnourdAssistant Professo at Department of Physical Education and Sport Sciences, Boj.C., Islamic Azad University, Bojnourd, Iran.

5 Assistant Professo at Department of Physical Education and Sport Sciences, Boj.C., Islamic Azad University, Bojnourd, Iran.

Abstract

The AMPK/SREBP-1c/ACC signaling pathway plays a crucial role in reducing hepatic lipid accumulation by inhibiting fat synthesis. This study investigated the effects of high-intensity interval training (HIIT) and ginger supplementation on this pathway in male Wistar rats with NAFLD.

Twenty-five rats were randomly divided into five groups: healthy control, disease control, exercise, ginger supplement, and a combination group. NAFLD was induced in 20 rats via a 12-week high-fat diet. Following confirmation of the disease, the respective groups received either daily ginger supplementation, an 8-week HIIT program, both, or no intervention. Gene expression of AMPK, SREBP-1c, and ACC was measured using Real-Time PCR.

The results showed a significant increase in AMPK gene expression and a significant decrease in SREBP-1c and ACC expression in all intervention groups compared to the disease control group. Conversely, the disease control group showed significantly lower AMPK and higher SREBP-1c/ACC expression compared to the healthy controls. No significant differences in gene expression changes were observed among the three intervention groups.

In conclusion, both HIIT and ginger supplementation, individually and combined, effectively modulate the AMPK/SREBP-1c/ACC pathway. This suggests that these interventions can prevent hepatic fat accumulation and the toxic complications of NAFLD, with no synergistic effect observed when combined.

Keywords

  1. Liu M, Park S. The role of PNPLA3 _rs738409 gene variant, lifestyle factors, and bioactive compounds in nonalcoholic fatty liver disease: a population-based and molecular approach towards healthy nutrition. Nutrients. 2024;16(8):1239.
  2. Zhai M, Zhang C, Cui J, Liu J, Li Y, Xie K, et al. Electromagnetic fields ameliorate hepatic lipid accumulation and oxidative stress: potential role of CaMKKβ/AMPK/SREBP-1c and Nrf2 pathways. BioMedical Engineering OnLine. 2023;22(1):51.
  3. Bai J, Yang T, Zhou Y, Xu W, Han S, Guo T, et al. Octacosanol modifies obesity, expression profile and inflammation response of hepatic tissues in high-fat diet mice. Foods. 2022;11(11):1606.
  4. Yan Q, Li C, Li J, Yao Y, Zhao J. Protective Effects of Isostrictiniin Against High-Fat, High-Sugar Diet-Induced Steatosis in MASLD Mice via Regulation of the AMPK/SREBP-1c/ACC Pathway. Nutrients. 2024;16(22):3876.
  5. Fu J, Liu C, Yang L, Zhang B, Zhou R, Deng C, et al. Effect of high-intensity interval training on clinical parameters in patients with metabolic dysfunction–associated steatotic liver disease: a systematic review and meta-analysis of randomized controlled trials. European Journal of Gastroenterology & Hepatology. 2025;37(7):789-98.
  6. Poon ET-C, Wongpipit W, Li H-Y, Wong SH-S, Siu PM, Kong AP-S, et al. High-intensity interval training for cardiometabolic health in adults with metabolic syndrome: a systematic review and meta-analysis of randomised controlled trials. British Journal of Sports Medicine. 2024;58(21):1267-84.
  7. Petersen MH, de Almeida ME, Wentorf EK, Jensen K, Ørtenblad N, Højlund K. High-intensity interval training combining rowing and cycling efficiently improves insulin sensitivity, body composition and VO2max in men with obesity and type 2 diabetes. Frontiers in endocrinology. 2022;13:1032235.
  8. Ghoreishi PS, Shams M, Nimrouzi M, Zarshenas MM, Lankarani KB, Fallahzadeh Abarghooei E, et al. The effects of ginger (Zingiber officinale Roscoe) on non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus: A randomized double-blinded placebo-controlled clinical trial. Journal of Dietary Supplements. 2024;21(3):294-312.
  9. Keshavarz F, Anoushirvani S, Arazi H, Afroundeh R, Golpasandi H. The effect of HIFT with ginger extract supplementation on the levels of some antioxidant enzymes in men with non-alcoholic fatty liver. Research in Exercise Nutrition. 2025;3(3):12-1.
  10. Zandi B, Abedi B. Effects of Aerobic Training with Ginger Consumption on Plasma Levels of Adipokine Glipican-4 and Hepatokine Fetuin- A in Rats with Non-alcoholic Fatty Livers. Iranian Journal of Nutrition Sciences and Food Technology. 2022;16(4):9-18.
  11. Nayebi far s, Ghasemi E. The Assessment of Changes in Liver Aminotransferases and Insulin Resistance Following 4 Weeks of High Intensity Interval Training and Ginger Supplementation in Active Middle Aged Men. Journal of Sabzevar University of Medical Sciences. 2021;28(1):106-14.
  12. Fatemi MS, Cheragh BS, Kheyrandish A. The effect of High-intensity interval training with Portulaca Oleracea Extract Supplementation on sirtuin 6 and insulin resistance in rats with non-alcoholic fatty liver disease. 2025.
  13. Abassi W, Ouerghi N, Hammami MB, Jebabli N, Feki M, Bouassida A, et al. High-intensity interval training reduces liver enzyme levels and improves MASLD-Related biomarkers in overweight/obese girls. Nutrients. 2025;17(1):164.
  14. Farahnia M, Hosseinabadi MR, Zarei M, Soltani M. The effect of high intensity interval training with Portulaca Oleracea supplementation on FXR and SREBP-1c in the liver tissue of rats with non-alcoholic fatty liver disease. Journal of Applied Health Studies in Sport Physiology. 2024;11(1):124-38.
  15. Tavakoli P, Jafary H, Yaghmaei P. The effect of ginger extract and vitamin K on serum levels of liver enzymes in NMRI mice with non-alcoholic fatty liver. Feyz Medical Sciences Journal. 2019;23(1):20-6.
  16. Ramezani Vavdare F, Nazarali P, Shakibaee A, Kazemi F. Effects of a period of moderate-intensity interval training (MIIT) with ginger supplementation on PGC-1α and ATPIF1 gene expression in gastrocnemius muscle of aged male rats. Iranian Journal of Physiology and Pharmacology. 2023;7:240-9.
  17. Kazemi M, Abdi A, Barari A, Mehrabani J. The effect of interval training and omega-3 on endoplasmic reticulum stress in the liver tissue of nonalcoholic fatty liver disease (NAFLD) rats. Medical Science Journal of Islamic Azad Univesity-Tehran Medical Branch. 2025;34(1):25-36.
  18. Khalesi M. Effect of a period of swimming exercise on Sirt1 and FoxO3a genes expression in lung tissue of wistar rats. Journal of Sabzevar University of Medical Sciences. 2018;25(2):251-8.
  19. Fang C, Pan J, Qu N, Lei Y, Han J, Zhang J, et al. The AMPK pathway in fatty liver disease. Frontiers in Physiology. 2022;13:970292.
  20. Li X, Zhang Y, Jin Q, Xia KL, Jiang M, Cui BW, et al. Liver kinase B1/AMP‐activated protein kinase‐mediated regulation by gentiopicroside ameliorates P2X7 receptor‐dependent alcoholic hepatosteatosis. British Journal of Pharmacology. 2018;175(9):1451-70.
  21. Bai Y, Li T, Liu J, Wang Y, Wang C, Ju S, et al. Aerobic exercise and vitamin E improve high-fat diet-induced NAFLD in rats by regulating the AMPK pathway and oxidative stress. European Journal of Nutrition. 2023;62(6):2621-32.
  22. Yu Y, Zhu G, Zhang Z, Wang H, Zeng L, Xia J, et al. Exercise ameliorates nonalcoholic fatty liver disease by reducing the IGFBP5 to IGF1 ratio to activate AMPK pathway. Scientific Reports. 2025;15(1):23083.
  23. Xu J, Jia W, Zhang G, Liu L, Wang L, Wu D, et al. Extract of Silphium perfoliatum L. improve lipid accumulation in NAFLD mice by regulating AMPK/FXR signaling pathway. Journal of Ethnopharmacology. 2024;327:118054.
  24. Li H, Dun Y, Zhang W, You B, Liu Y, Fu S, et al. Exercise improves lipid droplet metabolism disorder through activation of AMPK-mediated lipophagy in NAFLD. Life sciences. 2021;273:119314.
  25. Yin X, Liu Z, Wang J. Tetrahydropalmatine ameliorates hepatic steatosis in nonalcoholic fatty liver disease by switching lipid metabolism via AMPK-SREBP-1c-Sirt1 signaling axis. Phytomedicine. 2023;119:155005.
  26. Sturgeon K, Muthukumaran G, Ding D, Bajulaiye A, Ferrari V, Libonati JR. Moderate‐intensity treadmill exercise training decreases murine cardiomyocyte cross‐sectional area. Physiological reports. 2015;3(5):e12406.
  27. Aghaei Bahmanbeglou N, Sherafati Moghadam M, Amirahmadi M. The Effect of Ampk and P53 Proteins On Tor Pathway Following Endurance Training In The Left Ventricle Of The Heart Of Diabetic Rats By Streptozotocin And Nicotinamide. Iranian Journal of Diabetes and Metabolism. 2021;21(1):13-23.
  28. Mamashli F, Farajtabar Behrestaq S, Askari B, taghipour A, Askari A. Effects of Eight Weeks of Intense Aerobic Training and Cinnamon Extract on Gene Expression of SREBP-1c and LXRα in the Liver Tissue of Rats Fed with Fructose Diets. Iranian Journal of Nutrition Sciences and Food Technology. 2024;19(3):11-20.
  29. Ghoreishi F, Farajtabar Behrestaq S, Taghipoor asrami A, Habibian M. Effect of aerobic training and capsaicin on the expression of lipogenic genes SREBP-1c and FASN in liver tissue of obese rats. Journal of Ilam University of Medical Sciences. 2024;32(2):44-54.
  30. Yu W, Qiu J, Chen Y, Che X, Li X. Chrysanthemum morifolium extract improves metabolic dysfunction-associated fatty liver disease by regulating lipid metabolism. Scientific Reports. 2025;15(1):40069.
  31. Eftekharzadeh M, Atashak S, Azarbayjani MA, Moradi L, Rahmati-Ahmadabad S. The Effect of Aerobic Exercise on SREBP-1c Gene Expression in Skeletal Muscle in Obese Female Rats. Thrita. 2023;12(1):e138382.
  32. Hasanatuludhhiyah N, Mustika A, Kalanjati VP, Miftahussurur M, Uemura N. Acetyl-CoA Carboxylase Inhibitors for Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pharmaceuticals. 2025;18(9):1276.
  33. khalili E, Janat Alipour N, Meshkani R, Tolabi K, Emamgholipour S. FAS and ACC dysfunction in visceral Adipose Tissue. Payavard Salamat. 2020;14(2):96-107.
  34. Beretta M, Vancuylenburg CS, Shrestha R, Olzomer EM, Osborne B, Zhou M, et al. Isotype-selective roles of hepatic acetyl-CoA carboxylases in a mouse model of fatty liver disease. Molecular Metabolism. 2025:102264.
  35. Maleki S, Azarbayjani MA, Riyahi MS, Peeri M, Rahmati AS. The Effect of Aerobic Exercise and Ethanolic Extract of Rice Bran on The Expression of Acetyl-CoA Carboxylase and HMGCR Genes in the Liver Tissue of Rats Fed with a High-Fat Diet. Health. 2024;2(3):89-100.
  36. Salimi safar Z, Esmaeili M. The effect of 8 weeks HIIT training with ginger supplementation on IL-6 and PGE serum in young female taekwondo athletes. Research in Sport Sciences Education (RISSE). 2024;2(2):43-50.
  37. abbaspour f, Mousavi sadati Sk, Behdari R. Effect of Endurance Training with Ginger Supplementation on CRP and TNF-a in Young Girls Aged 20 to 30. Journal of Sabzevar University of Medical Sciences. 2020;27(2):219-26.
Journal of Exercise Physiology in Special Populations
Volume 3, Issue 1
April 2026
Pages 1-19