Effect of resveratrol on gluconeogenesis in exercise-induced fatigue rats

doi:10.12307/2023.960

Abstract

Abstract: BACKGROUND: Resveratrol is a natural antioxidant extracted from plants. Its mechanism of improving exercise-induced fatigue mainly focuses on the protective effect against oxidative stress and inflammation. In this study, the protective mechanism of resveratrol on exercise-induced fatigue was mainly discussed from the perspective of gluconeogenesis.
OBJECTIVE: To investigate the effect of resveratrol on gluconeogenesis in exercise-induced fatigue rats.
METHODS: After 1 week of adaptive training, male Sprague-Dawley rats were randomly divided into 4 groups with 12 rats in each group: blank control group, resveratrol group, exercise group, resveratrol + exercise group. Weight-bearing swimming training was used to simulate long-term medium-high intensity exercise. After swimming with a weight of 5% for 1 hour every day, 50 mg/kg resveratrol solution or the same volume of dimethyl sulfoxide solvent were given orally, 6 days a week, for a total of 6 weeks. Samples were collected 24 hours after the last exercise, and the levels of urea nitrogen, creatine kinase, blood glucose, liver glycogen and lactic acid and pyruvate in liver tissue were detected by the kit. The activity of phosphoenolpyruvate carboxykinase was detected by microassay, and the activity of glucose-6-phosphatase was detected by enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR was used to detect the gene expression of silent information regulator 1, cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α.
RESULTS AND CONCLUSION: In the exercise group, plasma urea nitrogen and creatine kinase levels of rats were significantly increased (both P < 0.05), liver lactate and pyruvate levels and lactate/pyruvate ratio were significantly increased (all P < 0.01), and blood glucose and liver glycogen contents were significantly decreased (both P < 0.01). Resveratrol supplementation could effectively improve the above conditions. Exercise significantly decreased the activities of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (P < 0.01, P < 0.05), and resveratrol supplementation significantly increased the activity of phosphoenolpyruvate carboxykinase in liver tissue (P < 0.01). The mRNA expression levels of silent information regulator 1, cAMP-response element binding protein and peroxisome proliferator-activated receptor-γ coactivator-1α in liver tissue of the exercise group were significantly decreased (all P < 0.01), while resveratrol supplementation could significantly increase the gene expression levels of this pathway. To conclude, resveratrol can relieve exercise-induced fatigue caused by long-term medium-high intensity exercise, and its mechanism may be related to up-regulating the gluconeogenesis regulatory pathway, improving rate-limiting enzyme activity, promoting liver gluconeogenesis, and increasing blood glucose and liver glycogen levels.

Key words: exercise-induced fatigue, resveratrol, gluconeogenesis, rate-limiting enzyme, rat

CLC Number:

Ruan Rong, Lou Xujia, Jin Qiguan, Zhang Libing, Xu Shang, Hu Yulong. Effect of resveratrol on gluconeogenesis in exercise-induced fatigue rats[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(8): 1229-1234.

Figures/Tables 5

References

[1] 田野. 运动生理学高级教程[M].北京:高等教育出版社,2003: 453-470.
[2] 张蕴琨,丁树哲. 运动生物化学[M].北京:高等教育出版社,2014: 145.
[3] GONZALEZ JT, FUCHS CJ, BETTS JA, et al. Liver glycogen metabolism during and after prolonged endurance-type exercise. Am J Physiol Endocrinol Metab. 2016;311(3):E543-E553.
[4] MULLER GY, MATOS FO, PEREGO JUNIOR JE, et al. High-intensity interval resistance training (HIIRT) improves liver gluconeogenesis from lactate in Swiss mice. Appl Physiol Nutr Metab. 2022;47(4):439-446.
[5] CHOI I, RICKERT E, FERNANDEZ M, et al. SIRT1 in Astrocytes Regulates Glucose Metabolism and Reproductive Function. Endocrinology. 2019; 160(6):1547-1560.
[6] SHE Y, SUN J, HOU P, et al. Time-restricted feeding attenuates gluconeogenic activity through inhibition of PGC-1α expression and activity. Physiol Behav. 2021;231:113313.
[7] 李先宽,李赫宇,李帅,等. 白藜芦醇研究进展[J]. 中草药,2016, 47(14):2568-2578.
[8] 杨海荣,李雪斌,劳贞贤,等. 白藜芦醇药理作用研究进展[J]. 中国老年学杂志, 2020,40(16):3572-3575.
[9] 郭瑞. 白藜芦醇抗疲劳作用及其机理研究[J]. 食品研究与开发, 2018,39(24):174-179.
[10] TUNG YT, WU MF, LEE MC, et al. Antifatigue Activity and Exercise Performance of Phenolic-Rich Extracts from Calendula officinalis, Ribes nigrum, and Vaccinium myrtillus. Nutrients. 2019;11(8):1715.
[11] HUANG WC, HSU YJ, WEI L, et al. Association of physical performance and biochemical profile of mice with intrinsic endurance swimming. Int J Med Sci. 2016;13(12):892-901.
[12] XIE Y, Li Z, WANG Y, et al. Effects of moderate-versus high-intensity swimming training on inflammatory and CD4(+) T cell subset profiles in experimental autoimmune encephalomyelitis mice. J Neuroimmunol. 2019;328:60-67.
[13] 贾瑞真,姜超,金其贯,等. 左旋肉碱、泛酸、辅酶Q_(10)联合干预有氧运动疲劳模型小鼠的作用及机制[J]. 中国组织工程研究, 2022,26(2):165-170.
[14] 李方,曹建民,翟鹏飞,等. 白藜芦醇调节NLRP3炎性小体改善力竭运动大鼠肾组织炎症损伤[J]. 陆军军医大学学报,2022,44(12): 1229-1236.
[15] 代朋乙,黄昌林. 运动性疲劳研究进展[J]. 解放军医学杂志,2016, 41(11):955-964.
[16] ZHANG X, YANG S, CHEN J, et al. Unraveling the Regulation of Hepatic Gluconeogenesis. Front Endocrinol (Lausanne). 2019;9:802.
[17] LEE MC, HSU YJ, LIN YQ, et al. Effects of Perch Essence Supplementation on Improving Exercise Performance and Anti-Fatigue in Mice. Int J Environ Res Public Health. 2022;19(3):1155.
[18] GIURIATO G, VENTURELLI M, MATIAS A, et al. Capsaicin and Its Effect on Exercise Performance, Fatigue and Inflammation after Exercise. Nutrients. 2022;14(2):232.
[19] 赵静. 运动疲劳机制及食源性抗疲劳活性成分研究进展[J]. 食品安全质量检测学报,2021,12(9):3565-3571.
[20] QIN LL, LU TF, QIN Y, et al. In Vivo Effect of Resveratrol-Loaded Solid Lipid Nanoparticles to Relieve Physical Fatigue for Sports Nutrition Supplements. Molecules. 2020;25(22):5302.
[21] LÓPEZ-SOLDADO I, GUINOVART JJ, DURAN J. Increased liver glycogen levels enhance exercise capacity in mice. J Biol Chem. 2021;297(2): 100976.
[22] BALTACI AK, DURAN MO, MOGULKOC R, et al. Resveratrol does not affect leptin while it has regulatory effects on liver glycogen levels in exercised and non-exercised rats. Int J Vitam Nutr Res. 2019;89(5-6): 303-308.
[23] 熊正英,张琳,武胜奇.白藜芦醇对大强度耐力训练大鼠部分生化指标的影响[J]. 武汉体育学院学报,2008,42(8):62-66.
[24] 浦钧宗, WASSERMAN K, WHIPP BJ,等.对常人运动中达无氧阈时动脉血乳酸、丙酮酸等指标变化的探讨[J]. 中国运动医学杂志, 1985(1):17-23+63.
[25] 沈文清,张强,张怡,等.不同方式急性运动结合二甲双胍改善 2型糖尿病小鼠血糖稳态及肝脏糖异生的作用[J]. 首都体育学院学报,2019,31(6):560-569.
[26] 韩锦铂,王一国. 肝脏糖异生的调控[J].中国细胞生物学学报, 2019,41(7):1216-1224.
[27] RAJAS F, GAUTIER-STEIN A, MITHIEUX G. Glucose-6 Phosphate, A Central Hub for Liver Carbohydrate Metabolism. Metabolites. 2019; 9(12):282.
[28] 陈娟娟. 人参果胶WGPA通过促进糖异生途径改善小鼠运动性疲劳的研究[D]. 长春:东北师范大学,2017.
[29] HUANG JP, TAGAWA T, MA SH, et al. Black Ginger (Kaempferia parviflora) Extract Enhances Endurance Capacity by Improving Energy Metabolism and Substrate Utilization in Mice. Nutrients. 2022;14(18): 3845.
[30] KOMINE S, MIYAZAKI T, ISHIKURA K, et al. Taurine supplementation enhances endurance capacity by delaying blood glucose decline during prolonged exercise in rats. Amino Acids. 2022;54(2):251-260.
[31] ZHANG WW, XUE R, MI TY, et al. Propofol ameliorates acute postoperative fatigue and promotes glucagon-regulated hepatic gluconeogenesis by activating CREB/PGC-1α and accelerating fatty acids beta-oxidation. Biochem Biophys Res Commun. 2022;586: 121-128.
[32] RODGERS JT, LERIN C, HAAS W. et al. Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1. Nature. 2005; 434:113-118.
[33] WANG T, WANG Y, LIU L, et al. Research progress on sirtuins family members and cell senescence. Eur J Med Chem. 2020;193:112207.
[34] RODGERS JT, PUIGSERVER P. Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. Proc Natl Acad Sci U S A. 2007;104(31):12861-12866.
[35] PARK JM, KIM TH, BAE JS, et al. Role of resveratrol in FOXO1-mediated gluconeogenic gene expression in the liver. Biochem Biophys Res Commun. 2010;403(3-4):329-334.
[36] WEI YJ, WANG JF, CHENG F, et al. miR-124-3p targeted SIRT1 to regulate cell apoptosis, inflammatory response, and oxidative stress in acute myocardial infarction in rats via modulation of the FGF21/CREB/PGC1alpha pathway. J Physiol Biochem. 2021;77(4):577-587.
[37] LI BX, GARDNER R, XUE C, et al. Systemic Inhibition of CREB is Well-tolerated in vivo. Sci Rep. 2016;6(1):34513.
[38] THIEL G, ROSSLER OG. Resveratrol stimulates cyclic AMP response element mediated gene transcription. Mol Nutr Food Res. 2016;60(2): 256-265.
[39] 吴遵桃.生命早期铅致SD大鼠学习记忆损伤及白藜芦醇的保护作用[D].郑州:郑州大学,2020.
[40] 乔爱君,左瑾,刘晓军,等. Sirt1基因的研究进展[J]. 中国医学科学院学报,2009,31(6):782-785.
[41] HERZIG S, LONG FX, JHALA US, et al. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature. 2001;413 (6852):179-183.
[42] 韩向晖,季光.肝脏糖异生的分子机制研究进展[J]. 世界华人消化杂志,2008,16(32):3659-3665.
[43] 娄旭佳.白藜芦醇对运动性疲劳大鼠线粒体能量代谢的影响[D].扬州:扬州大学,2022.
[44] HAASE TN, RINGHOLM S, LEICK L, et al. Role of PGC-1alpha in exercise and fasting-induced adaptations in mouse liver. Am J Physiol Regul Integr Comp Physiol. 2011;301(5):R1501-R1509.