Document Type : Research Paper I Open Access I Released under CC BY-NC 4.0 license


1 Department of Sports Physiology, Faculty of Sports Sciences, Ferdowsi University of Mashhad, Mashhad, Iran.

2 Corresponding Author, Department of Sports Physiology, Faculty of Sports Sciences, Ferdowsi University of Mashhad, Mashhad, Iran.

3 Department of Exercise Physiology, Faculty of Sport Science, Hakim Sabzevari University, Sabzevar, Iran


Introduction: Obesity and overweight are metabolic disorders in which fat tissue levels are influential in this disorder. The current research aimed to investigate the effect of eight weeks of endurance, resistance, and high-intensity interval training on the SREBP-1 and 12.13.diHome gene expression in male obese Wistar rats.
Methods: In the current study, 36 obese male Wistar rats (eight weeks old rats with a weight of 325 ± 40 grams) were randomly divided into four Endurance (n=10), Resistance (n=8), High-Intensity Interval Training (n=10) and Control (n=8) groups. The rats in the experimental groups performed five sessions of endurance training at an intensity of 70-80% of the maximum speed, resistance training at an intensity of 50-120% of the body weight, and HIIT at an intensity of 85-90% of the maximum speed for eight weeks. To measure SREBP-1 and 12.13.diHome gene expression, the Real Time-PCR method was used. The statistical method of one-way analysis of variance with Tukey's post hoc test was used to determine the difference between groups at a significant level of α= 0.05.
Results: The results of the present study showed that all three training models of endurance, resistance, and HIIT caused a significant increase in the expression of the 12.13.diHome gene and a significant decrease in SREBP-1 compared with the control group (P<0.05), but no significant difference was observed among the experimental groups (P>0.05).
Conclusion: To lose weight, it is suggested to use endurance, resistance, and HIIT training to reduce the expression of the SREBP-1 gene and increase 12.13.diHome, which are factors influencing lipolysis and lipogenesis.


Main Subjects

  1. Cimini FA, Barchetta I, Ciccarelli G, Leonetti F, Silecchia G, Chiappetta C, Di Cristofano C, Capoccia D, Bertoccini L, Ceccarelli V, Carletti R. Adipose tissue remodelling in obese subjects is a determinant of presence and severity of fatty liver disease. Diabetes/Metabolism Research and Reviews. 2021 Jan;37(1):e3358.

2.Ramos LF, Silva CM, Pansa CC, Moraes KC. Non-alcoholic fatty liver disease: molecular and cellular interplays of the lipid metabolism in a steatotic liver. Expert Review of Gastroenterology & Hepatology. 2021 Jan 2;15(1):25-40.

3.Yan F, Wang Q, Lu M, Chen W, Song Y, Jing F, Guan Y, Wang L, Lin Y, Bo T, Zhang J. Thyrotropin increases hepatic triglyceride content through upregulation of SREBP-1c activity. Journal of Hepatology. 2014 Dec 1;61(6):1358-64.

  1. 4. Zhou Z, Liang S, Zhou Z, Liu J, Zhang J, Meng X, Zou F, Zhao H, Yu C, Cai S. TGF-β1 promotes SCD1 expression via the PI3K-Akt-mTOR-SREBP1 signaling pathway in lung fibroblasts. Respiratory Research. 2023 Dec;24(1):1-5. 1186/s12931-023-02313-9
  2. Wu L, Guo T, Deng R, Liu L, Yu Y. Apigenin ameliorates insulin resistance and lipid accumulation by endoplasmic reticulum stress and SREBP-1c/SREBP-2 pathway in palmitate-induced HepG2 cells and high-fat diet–fed mice. Journal of Pharmacology and Experimental Therapeutics. 2021 Apr 1;377(1):146-56.
  3. Jayachandran M, Zhang T, Wu Z, Liu Y, Xu B. Isoquercetin regulates SREBP-1C via AMPK pathway in skeletal muscle to exert antihyperlipidemic and anti-inflammatory effects in STZ induced diabetic rats. Molecular Biology Reports. 2020 Jan;47:593-602.
  4. Nakamuta M, Fujino T, Yada R, Yada M, Yasutake K, Yoshimoto T, Harada N, Higuchi N, Kato M, Kohjima M, Taketomi A. Impact of cholesterol metabolism and the LXRα-SREBP-1c pathway on nonalcoholic fatty liver disease. International journal of molecular medicine. 2009 May 1;23(5):603-8.
  5. 8. Sun Q, Yu X, Peng C, Liu N, Chen W, Xu H, Wei H, Fang K, Dong Z, Fu C, Xu Y. Activation of SREBP-1c alters lipogenesis and promotes tumor growth and metastasis in gastric cancer. Biomedicine & Pharmacotherapy. 2020 Aug 1;128:110274..
  6. Abukhalil MH, Hussein OE, Bin-Jumah M, Saghir SA, Germoush MO, Elgebaly HA, Mosa NM, Hamad I, Qarmush MM, Hassanein EM, Kamel EM. Farnesol attenuates oxidative stress and liver injury and modulates fatty acid synthase and acetyl-CoA carboxylase in high cholesterol-fed rats. Environmental Science and Pollution Research. 2020 Aug;27:30118-32.
  7. Abukhalil MH, Hussein OE, Bin-Jumah M, Saghir SA, Germoush MO, Elgebaly HA, Mosa NM, Hamad I, Qarmush MM, Hassanein EM, Kamel EM. Farnesol attenuates oxidative stress and liver injury and modulates fatty acid synthase and acetyl-CoA carboxylase in high cholesterol-fed rats. Environmental Science and Pollution Research. 2020 Aug;27:30118-32..
  8. Zhang W, Li JY, Wei XC, Wang Q, Yang JY, Hou H, Du ZW, Wu XA. Effects of dibutyl phthalate on lipid metabolism in liver and hepatocytes based on PPARα/SREBP-1c/FAS/GPAT/AMPK signal pathway. Food and Chemical Toxicology. 2021 Mar 1;149:112029.
  9. Sharma A, Anand SK, Singh N, Dwarkanath A, Dwivedi UN, Kakkar P. Berbamine induced activation of the SIRT1/LKB1/AMPK signaling axis attenuates the development of hepatic steatosis in high-fat diet-induced NAFLD rats. Food & Function. 2021;12(2):892-909.
  10. Oh S, Shida T, Yamagishi K, Tanaka K, So R, Tsujimoto T, Shoda J. Moderate to vigorous physical activity volume is an important factor for managing nonalcoholic fatty liver disease: a retrospective study. Hepatology. 2015 Apr;61(4):1205-15..
  11. Cintra DE, Ropelle ER, Vitto MF, Luciano TF, Souza DR, Engelmann J, Marques SO, Lira FS, de Pinho RA, Pauli JR, De Souza CT. RETRACTED: Reversion of hepatic steatosis by exercise training in obese mice: the role of sterol regulatory element-binding protein-1c..
  12. Yang J, Sáinz N, Félix-Soriano E, Gil-Iturbe E, Castilla-Madrigal R, Fernández-Galilea M, Martínez JA, Moreno-Aliaga MJ. Effects of long-term DHA supplementation and physical exercise on non-alcoholic fatty liver development in obese aged female mice. Nutrients. 2021 Feb 3;13(2):501.
  13. Ebrahimi.M, Fathi, R, Ansari-Pirsaraei, Z, Talebigerkani.E. Relative expression of key lipid metabolism genes following high-fat diet and aerobic exercise in rat liver. Sport physiology. 2017;34(9):201-16.[in persian].
  14. Hedayati katouli A, Azarbayjani M, Banaeifar A, Arshadi S. The Effect of Aerobic Training and Adenosine on the Expression of SREBP-1C and A1 Receptor in Hepatic Fat-fed Rats. Iranian J Nutr Sci Food Technol 2019; 14 (1) :1-9[in persian].
  15. Jeong S. Regulation of PPAR and SREBP-1C Through Exercise in White Adipose Tissue of Female C57BL/6J Mice. 대한의생명과학회지. 2012 Sep;18(3):227-36.
  16. Haun CT, Mobley CB, Vann CG, Romero MA, Roberson PA, Mumford PW, Kephart WC, Healy JC, Patel RK, Osburn SC, Beck DT. Soy protein supplementation is not androgenic or estrogenic in college-aged men when combined with resistance exercise training. Scientific reports. 2018 Jul 24;8(1):11151..
  17. Asano M, Iwagaki Y, Sugawara S, Kushida M, Okouchi R, Yamamoto K, Tsuduki T. Effects of Japanese diet in combination with exercise on visceral fat accumulation. Nutrition. 2019 Jan 1;57:173-82.
  18. Dobrzyn P, Pyrkowska A, Jazurek M, Szymanski K, Langfort J, Dobrzyn A. Endurance training-induced accumulation of muscle triglycerides is coupled to upregulation of stearoyl-CoA desaturase 1. Journal of Applied Physiology. 2010;109(6):1653-61
  19. Ziaaldini MM, Koltai E, Csende Z, Goto S, Boldogh I, Taylor AW, Radak Z. Exercise training increases anabolic and attenuates catabolic and apoptotic processes in aged skeletal muscle of male rats. Experimental gerontology. 2015 Jul 1;67:9-14.
  20. Symonds M, Bloor I, Galvez F, Domfeh E, Maicas B, Poston L, et al. Effect of a dietary and exercise intervention during pregnancy and lactation on white adipose tissue gene profiles and adiposity with maternal obesity. The FASEB Journal. 2016;30:1214.3-.3.
  21. Sui SX, Williams LJ, Holloway-Kew KL, Hyde NK, Pasco JA. Skeletal muscle health and cognitive function: A narrative review. International journal of molecular sciences. 2020;22(1):255.
  22. Hildreth K, Kodani SD, Hammock BD, Zhao L. Cytochrome P450-derived linoleic acid metabolites EpOMEs and DiHOMEs: a review of recent studies. The Journal of nutritional biochemistry. 2020;86:108484.
  23. Lynes MD, Leiria LO, Lundh M, Bartelt A, Shamsi F, Huang TL, et al. The cold-induced lipokine 12, 13-diHOME promotes fatty acid transport into brown adipose tissue. Nature medicine. 2017;23(5):631-7.
  24. Badi I, Antoniades C. Brown Adipose Tissue and the Take (12, 13-di) HOME Message to the Heart. Am Heart Assoc; 2021. p. 160-2.
  25. Pinckard KM, Shettigar VK, Wright KR, Abay E, Baer LA, Vidal P, et al. A novel endocrine role for the BAT-released lipokine 12, 13-diHOME to mediate cardiac function. Circulation. 2021;143(2):145-59.
  26. Foryst-Ludwig A, Kreissl MC, Benz V, Brix S, Smeir E, Ban Z, Januszewicz E, Salatzki J, Grune J, Schwanstecher AK, Blumrich A. Adipose tissue lipolysis promotes exercise-induced cardiac hypertrophy involving the lipokine C16: 1n7-palmitoleate. Journal of Biological Chemistry. 2015 Sep 25;290(39):23603-15
  27. Stanford KI, Lynes MD, Takahashi H, Baer LA, Arts PJ, May FJ, et al. 12, 13-diHOME: an exercise-induced lipokine that increases skeletal muscle fatty acid uptake. Cell metabolism. 2018;27(5):1111-20. e3.
  28. Morville T, Sahl RE, Moritz T, Helge JW, Clemmensen C. Plasma metabolome profiling of resistance exercise and endurance exercise in humans. Cell reports. 2020;33(13):108554.
  29. Grapov D, Fiehn O, Campbell C, Chandler CJ, Burnett DJ, Souza EC, Casazza GA, Keim NL, Hunter GR, Fernandez JR, Garvey WT. Impact of a weight loss and fitness intervention on exerciseassociated plasma oxylipin patterns in obese, insulinresistant, sedentary women. Physiological reports. 2020 Sep;8(17):e14547.
  30. Steki A, Valipour V, Ghahramanlo E, Kargarfard M. The effect of endurance training in air pollution on the expression of brain cortex PGC-1α and Atf2 genes in Wistar male rats. KAUMS Journal (FEYZ). 2019;23(6):615-26 .[in persian].
  31. Karbasi S, Zaeemi M, Mohri M, Rashidlamir A, Moosavi Z. Effects of testosterone enanthate and resistance training on myocardium in Wistar rats; clinical and anatomical pathology. Andrologia. 2018 Apr;50(3):e12908..
  32. Norouzi Moin, Sadegh Yabas *, Pakdehimhadtseh Aksir, Turabi Ghasem. 1400. The effect of eight weeks of intense intermittent exercise and caffeine consumption on the expression of glycogen synthase and the amount of liver glycogen in large diabetic rats. Medical Scholar 156. 41-55.]in persian].
  33. Ikeda S, Miyazaki H, Nakatani T, Kai Y, Kamei Y, Miura S, Tsuboyama-Kasaoka N, Ezaki O. Up-regulation of SREBP-1c and lipogenic genes in skeletal muscles after exercise training. Biochemical and biophysical research communications. 2002 Aug 16;296(2):395-400.
  34. Chenfei Z, Haizhen Y, Jie X, Na Z, Bo X. Effects of aerobic exercise on hippocampal SUMOylation in APP/PS1 transgenic mice. Neuroscience Letters. 2022 Jan 10;767:136303.
  35. Egan B, Sharples AP. Molecular responses to acute exercise and their relevance for adaptations in skeletal muscle to exercise training. Physiological Reviews. 2023 Jul 1;103(3):2057-170 10.1152/physrev.00054.2021
  36. Ghiasi S, Bashiri J, Pourrazi H, Jadidi RP. The Effect of High-Intensity Interval Training and Coenzyme Q10 on the Expression of Hepatic IRS-2 and SREBP1 Proteins in Obese Male Rats. Gene, Cell and Tissue. 2021;8(4). .[in persian].
  37. Bae JY. Resistance exercise regulates hepatic lipolytic factors as effective as aerobic exercise in obese mice. International Journal of Environmental Research and Public Health. 2020 Nov;17(22):8307.
  38. Ebrahimi M, Fathi R, Ansari Pirsarii Z, Talebi-Garakani E. Relative gene expression of key genes involved in lipid metabolism, following high fat diet and moderate and high intensity aerobic training in rat’s liver. Sport Physiology. 2017;9(34):201-16.
  39. Azarbayjani M, Banaeifar A, Arshadi S. The Effect of Aerobic Training and Adenosine on the Expression of SREBP-1C and A1 Receptor in Hepatic Fat-fed Rats. Iranian Journal of Nutrition Sciences & Food Technology. 2019;14(1):1-9. .[in persian].
  40. Shahouzehi B, Masoumi-Ardakani Y, Nazari-Robati M, Aminizadeh S. The Effect of High-intensity Interval Training and L-carnitine on the Expression of Genes Involved in Lipid and Glucose Metabolism in the Liver of Wistar Rats. Brazilian Archives of Biology and Technology. 2022;66. .[in persian].
  41. Zarei F, Sherafati Moghadam M, Shabani M, Jokar M. the effects of 4 weeks high intensity interval training on mammalian rapamycin target protein (mtor) and sterol transcription factor regulatory protein-1 (srebp1) proteins content in diabetics obese rats adipose tissue. Iranian Journal of Diabetes and Metabolism. 2020;19(1):26-35. . .[in persian].
  42. Teixeira GR, Mendes LO, Veras ASC, Thorpe HHA, Fávaro WJ, de Almeida Chuffa LG, et al. Physical resistance training-induced changes in lipids metabolism pathways and apoptosis in prostate. Lipids in Health and Disease. 2020;19(1):1-9. 10.1186/s12944-020-1195-0
  43. Nadeau KJ, Ehlers LB, Aguirre LE, Moore RL, Jew KN, Ortmeyer HK, Hansen BC, Reusch JE, Draznin B. Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle. American Journal of Physiology-Endocrinology and Metabolism. 2006 Jul;291(1):E90-8. 10.1152/ajpendo.00543.2005
  44. Jokar M, Zarei F, Sharafati M*, Alizadeh P. H. . The effect of 8 weeks of endurance training on the content of mTOR and SREBP1 proteins in the subcutaneous fat tissue of obese male Spraguedauli rats with type 2 diabetes. Shahid Sadougi University of Medical Sciences Yazd. 2019 . 2755-2765. .[in persian].
  45. Yu Z, Feng Z, Fu L, Wang J, Li C, Zhu H, Xie T, Zhou J, Zhou L, Zhou X. Qingluotongbi formula regulates the LXRα-ERS-SREBP-1c pathway in hepatocytes to alleviate the liver injury caused by Tripterygium wilfordii Hook. f. Journal of Ethnopharmacology. 2022 Apr 6;287:114952.


  1. Szántó M, Gupte R, Kraus WL, Pacher P, Bai P. PARPs in lipid metabolism and related diseases. Progress in Lipid Research. 2021 Nov 1;84:101117.
  2. Vertegaal AC. Signalling mechanisms and cellular functions of SUMO. Nature Reviews Molecular Cell Biology. 2022 Nov;23(11):715-31
  3. Gehlert S, Klinz FJ, Willkomm L, Schiffer T, Suhr F, Bloch W. Intense resistance exercise promotes the acute and transient nuclear translocation of small ubiquitin-related modifier (SUMO)-1 in human myofibres. International Journal of Molecular Sciences. 2016 Apr 29;17(5):646.
  4. Udomsinprasert W, Honsawek S, Poovorawan Y. Adiponectin as a novel biomarker for liver fibrosis. World journal of hepatology. 2018 Oct 10;10(10):708.

  1. Liu Y, Li Y, Liang J, Sun Z, Wu Q, Liu Y, Sun C. Leptin: an entry point for the treatment of peripheral tissue fibrosis and related diseases. International Immunopharmacology. 2022 May 1;106:108608.

  1. London E, Stratakis CA. The regulation of PKA signaling in obesity and in the maintenance of metabolic health. Pharmacology & Therapeutics. 2022 Jan 17:108113.

  1. 55. Leandro CG, Levada AC, Hirabara SM, MANHAS-DE-CASTRO RA, De-Castro CB, Curi R, Pithon-Curi TC. Aprogram of moderate physical training for wistar rats based on maximal oxygen consumption. The Journal of Strength & Conditioning Research. 2007 Aug 1;21(3):751-6.