Effect of Aerobic Physical Activity While Fasting on Liver Lipophagy-Related Factors (ULK1 and LC3-II) in Male Wistar Rats

Document Type : Original Article


1 PhD Student, Department of Physical Education & Sports Sciences, Aliabad Katoul Branch, Islamic Azad University, Aliabad Katoul, Iran.

2 Assistant Professor, Department of Physical Education & Sports Sciences, Aliabad Katoul Branch, Islamic Azad University, Aliabad Katoul, Iran.

3 Assistant Professor of Sports Physiology, Department of Physical Education, Gorgan Branch, Islamic Azad University, Gorgan, Iran.



Background and Objectives ULK1 and LC3-II are factors related to liver lipophagy. The purpose of this research was to investigate the effect of four weeks of aerobic training in fasting state on factors related to liver lipophagy (ULK1 and LC3-II) in male Wistar rats. Subjects and Methods In this experimental research, 30 male Wistar rats were randomly divided into the following groups: control, fasting, 3 days of training, 5 days of training, fasting + 3 days of training, and fasting + 5 days of training. Unlike other rats that had 24-hour access to food, the fasting rats received the same amount of nutrition in 10 hours. Continuous aerobic running on a treadmill was performed for 4 weeks with a frequency of 3 and 5 sessions per week in both feeding and fasting conditions. Statistical analysis was done by SPSS using one-way variance analysis test and LSD. Significance level was set at P < 0.05. Results The increase of LC3-II in the groups of fasting + 3 days of training and fasting + 5 days training was significant compared to fasting and 3 days training groups (P < 0.05). Also, the increase of ULK1 in the groups of 3 days of training and fasting + 3 days of training was significant compared to the fasting group, and the changes of ULK1 were significantly higher in fasting + 3 days of training group than in the fasting + 5 days training group (P < 0.05). Conclusion It can be said that aerobic training in fasting mode increases liver lipophagy and the expression of ULK1 and LC3-II genes is different compared to the amount of weekly activity.


Main Subjects

[1] Jensen-Cody SO, Potthoff MJ. Hepatokines and metabolism: Deciphering communication from the liver. Molecular metabolism. 2021 Feb 1;44:101138. [10.1016/j.molmet.2020. 101138 ] [PMID]
[2] Ghalavand A, Ghobadi MR, Motamedi P, Delaramnasab M. Reduction of fetuin B in adaptation to pyramidal aerobic exercises and its role in modulating insulin resistance and serum aminotransferases in patients with type 2 diabetes. EBNESINA. 2023 Mar 10;25(1):13-20. [Link]
[3] Schulze RJ, Drižytė K, Casey CA, McNiven MA. Hepatic lipophagy: new insights into autophagic catabolism of lipid droplets in the liver. Hepatology communications. 2017 Jul;1(5):359-69. [10.1002/hep4.1056 ][PMID]
[4] Zhang S, Peng X, Yang S, Li X, Huang M, Wei S, Liu J, He G, Zheng H, Yang L, Li H. The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders. Cell Death & Disease. 2022 Feb 8;13(2):132. [10.1038/s41419-022-04593-3 ][PMID]
[5] Masuda M, Yoshida-Shimizu R, Mori Y, Ohnishi K, Adachi Y, Sakai M, Kabutoya S, Ohminami H, Yamanaka-Okumura H, Yamamoto H, Miyazaki M. Sulforaphane induces lipophagy through the activation of AMPK-mTOR-ULK1 pathway signaling in adipocytes. The Journal of Nutritional Biochemistry. 2022 Aug 1;106:109017. [10.1016/j.jnutbio.2022.109017 ][PMID]
[6] Zachari M, Ganley IG. The mammalian ULK1 complex and autophagy initiation. Essays in biochemistry. 2017 Dec 12;61(6):585-96. [10.1042/EBC20170021 ][PMID]
[7] Schmitz KJ, Ademi C, Bertram S, Schmid KW, Baba HA. Prognostic relevance of autophagy-related markers LC3, p62/sequestosome 1, Beclin-1 and ULK1 in colorectal cancer patients with respect to KRAS mutational status. World journal of surgical oncology. 2016 Dec;14(1):1-3.. [10.1186/s12957-016-0946-x ][PMID]
[8] Ma YN, Jiang X, Tang W, Song P. Influence of intermittent fasting on autophagy in the liver. BioScience Trends. 2023 Oct 31;17(5):335-55. [10.5582/bst.2023.01207 ][PMID]
[9] Noland RC. Exercise and regulation of lipid metabolism. Progress in molecular biology and translational science. 2015 Jan 1;135:39-74. [10.1016/bs.pmbts.2015.06.017 ][PMID]
[10] Li H, Dun Y, Zhang W, You B, Liu Y, Fu S, Qiu L, Cheng J, Ripley-Gonzalez JW, Liu S. Exercise improves lipid droplet metabolism disorder through activation of AMPK-mediated lipophagy in NAFLD. Life sciences. 2021 May 15;273:119314. [10.1016/j. lfs.2021.119314 ][PMID]
[11] Li R, Li G, Hai Y, Li T, Bian Y, Ma T. The effect of aerobic exercise on the lipophagy of adipose tissue in obese male mice. Chemistry and Physics of Lipids. 2022 Sep 1;247:105225. [10.1016/j.chemphyslip.2022.105225 ][PMID]
[12] Su P, Chen JG, Tang DH. Exercise against nonalcoholic fatty liver disease: Possible role and mechanism of lipophagy. Life Sciences. 2023 Jun 9:121837. [10.1016/j.lfs.2023.121837 ][PMID]
[13] Alex S, Boss A, Heerschap A, Kersten S. Exercise training improves liver steatosis in mice. Nutrition & metabolism. 2015 Dec;12(1):1-1. [10.1186/s12986-015-0026-1 ][PMID]
[14] Dethlefsen MM, Bertholdt L, Gudiksen A, Stankiewicz T,
Bangsbo J, van Hall G, Plomgaard P, Pilegaard H. Training state and skeletal muscle autophagy in response to 36 h of fasting. Journal of Applied Physiology. 2018 Nov 1;125(5):1609-19. [10.1152/japplphysiol.01146.2017 ][PMID]
[15] Santos-Alves E, Marques-Aleixo I, Rizo-Roca D, Torrella JR, Oliveira PJ, Magalhães J, Ascensão A. Exercise modulates liver cellular and mitochondrial proteins related to quality control signaling. Life sciences. 2015 Aug 15;135:124-30. [10.1016/j. lfs.2015.06.007 ][PMID]
[16] Schneider JL, Cuervo AM. Autophagy and human disease: emerging themes. Current opinion in genetics & development. 2014 Jun 1;26:16-23. [10.1016/j.gde.2014.04.003 ] [PMID]
[17] Vainshtein A, Hood DA. The regulation of autophagy during exercise in skeletal muscle. Journal of Applied Physiology. 2016 Mar 15;120(6):664-73. [10.1152/japplphysiol.00550.2015 ][PMID]
[18] Bagherniya M, Butler AE, Barreto GE, Sahebkar A. The effect of fasting or calorie restriction on autophagy induction: A review of the literature. Ageing research reviews. 2018 Nov 1;47:183-97. [10.1016/j.arr.2018.08.004 ][PMID]
[19] Møller AB, Vendelbo MH, Christensen B, Clasen BF, Bak AM, Jørgensen JO, Møller N, Jessen N. Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle. Journal of Applied Physiology. 2015 Apr 15;118(8):971-9. [10.1152/japplphysiol.01116.2014 ][PMID]
[20] Laker RC, Drake JC, Wilson RJ, Lira VA, Lewellen BM, Ryall KA, Fisher CC, Zhang M, Saucerman JJ, Goodyear LJ, Kundu M. Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy. Nature communications. 2017 Sep 15;8(1):548. [10.1038/ s41467-017-00520-9 ][PMID]
[21] Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nature cell biology. 2011 Feb;13(2):132-41. [10.1038/ncb2152 ][PMID]
[22] Ruderman NB, Park H, Kaushik VK, Dean D, Constant S, Prentki M, Saha AK. AMPK as a metabolic switch in rat muscle, liver and adipose tissue after exercise. Acta Physiologica Scandinavica. 2003 Aug;178(4):435-42. [10.1046/j.1365-201X.2003.01164.x ][PMID]
[23] Lu Q, Wang PS, Yang L. Golgi-associated Rab GTPases implicated in autophagy. Cell & Bioscience. 2021 Dec;11:1-9. [10.1186/s13578-021-00543-2 ][PMID]
[24] da Rocha AL, Pinto AP, Bedo BL, Morais GP, Oliveira LC, Carolino RO, Pauli JR, Simabuco FM, de Moura LP, Ropelle ER, Cintra DE. Exercise alters the circadian rhythm of REV-ERB-α and downregulates autophagy-related genes in peripheral and central tissues. Scientific Reports. 2022 Nov 21;12(1):20006. [10.1038/s41598-022-24277-4 ][PMID]
[25] Zou L, Liao M, Zhen Y, Zhu S, Chen X, Zhang J, Hao Y, Liu B. Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications. Acta Pharmaceutica Sinica B. 2022 Oct 1;12(10): 3743-82. [10.1016/j.apsb.2022.06.004 ][PMID]
[26] Mizushima N. The role of the Atg1/ULK1 complex in autophagy regulation. Current opinion in cell biology. 2010 Apr 1;22(2):132-9. [10.1016/j.ceb.2009.12.004 ][PMID]