The effect of endurance training on lipid metabolism in liver of prediabetic mice

Document Type : Research Paper

Authors

1 Department of Sports Physiology, Faculty of Sports Sciences, University of Isfahan, Isfahan, Iran.

2 Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

10.22080/jaep.2023.24794.2125

Abstract

Objectives: Prediabetes is a risk factor in diabetes and therefore a healthy lifestyle is important to prevent pre-diabetes. This study aimed to determine the effect of endurance training on hepatic lipid metabolism in prediabetic C57BL/6 male mice.
Methods: 21 mice were randomly divided into two groups. One was fed a normal diet (n=7, ND), and the other was fed a high-fat diet (n=14, HFD) for 12 weeks. After 12 weeks of initial maintenance, HFD s were subjected to a glucose tolerance test (GTT) and they were divided into two groups: exercise (EX) and pre-diabetes (preD). The training group trained for 45 minutes, 5 days a week, for 10 weeks. 24 hours before sacrifice, weighing and GTT were performed, and then the plasma and liver were obtained. The values of acetyl cocarboxylase beta (ACC2), carnitine palmitol transferase 1 (CPT1) and peroxisome receptor alpha were used to evaluate beta oxidation. Data interpretation was done using one-way analysis of variance with a significance level of p<0.05.
Results: In preD, weight, glucose, insulin, insulin resistance, and lipid profile experienced a significant increase compared to ND. In the EX, the mentioned factors were associated with a significant decrease (p < 0.01). CPT1 protein concentration, as a key factor of β-oxidation, decreased in preD the group, and ACC2, which is its inhibitor, increased. Endurance training improved fatty acid metabolism in the liver by reversing the expression process of these factors.
Conclusion: Generally, preD caused changes associated with β-oxidation in the liver, while it seems that endurance training improved all. These findings show that regular exercise is probably an effective nonpharmacological approach for pre-diabetes.

Keywords


##Wei Y, Hong Y, Hou P, Xu X. Effect of sugar-free Qishan granules on glucose and lipid metabolism and insulin resistance in a rat model of prediabetes. Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan. 2019;39(4):535-41##Sabag A, Way KL, Sultana RN, Keating SE, Gerofi JA, Chuter VH, et al. The Effect of a Novel Low-Volume Aerobic Exercise Intervention on Liver Fat in Type 2 Diabetes: A Randomized Controlled Trial. Diabetes care. 2020;43(10):2371-8##Zou Y, Qi Z. Understanding the Role of Exercise in Nonalcoholic Fatty Liver Disease: ERS-Linked Molecular Pathways. Mediators of inflammation. 2020;2020:6412916.## Hoene M, Li J, Li Y, Runge H, Zhao X, Häring HU, et al. Muscle and liver-specific alterations in lipid and acylcarnitine metabolism after a single bout of exercise in mice. Scientific reports. 2016;6:22218.## Li YP, Xiao J, Liang X, Pei Y, Han XF, Li CX, et al. DPP-4 inhibition resembles exercise in preventing type 2 diabetes development by inhibiting hepatic protein kinase C(ε) expression in a mouse model of hyperinsulinemia. The Journal of international medical research. 2020;48(6):300060520934635.## Bacchi E, Negri, C., Targher, G., Faccioli, N., Lanza, M., Zoppini, G., Zanolin, E., Schena, F., Bonora, E. and Moghetti, P. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 randomized trial). Hepatology. 2013;58:1287-95.## Cheng S, Ge J, Zhao C, Le S, Yang Y, Ke D, et al. Effect of aerobic exercise and diet on liver fat in pre-diabetic patients with non-alcoholic-fatty-liver-disease: A randomized controlled trial. Scientific reports. 2017;7(1):15952.## Iozzo P, Takala T, Oikonen V, Bergman J, Grönroos T, Ferrannini E, et al. Effect of training status on regional disposal of circulating free fatty acids in the liver and skeletal muscle during physiological hyperinsulinemia. Diabetes care. 2004;27(9):2172-7.## Rowan CP, Riddell MC, Gledhill N, Jamnik VK. Aerobic Exercise Training Modalities and Prediabetes Risk Reduction. Medicine and science in sports and exercise. 2017;49(3):403-12.##    Rui L. Energy metabolism in the liver. Comprehensive Physiology. 2014;4(1):177-97.## Valdecantos MP, Pérez-Matute P, Prieto-Hontoria P, Moreno-Aliaga MJ, Martínez JA. Impact of dietary lipoic acid supplementation on liver mitochondrial bioenergetics and oxidative status on normally fed Wistar rats. International journal of food sciences and nutrition. 2019;70(7):834-44.## van der Leij FR, Bloks VW, Grefhorst A, Hoekstra J, Gerding A, Kooi K, et al. Gene expression profiling in livers of mice after acute inhibition of beta-oxidation. Genomics. 2007;90(6):680-9.## Kojta I, Zabielski P, Roszczyc-Owsiejczuk K, Imierska M, Sokołowska E, Błachnio-Zabielska A. GPAT Gene Silencing in Muscle Reduces Diacylglycerols Content and Improves Insulin Action in Diet-Induced Insulin Resistance. International journal of molecular sciences. 2020;21(19)## Murase T, Misawa K, Minegishi Y, Aoki M, Ominami H, Suzuki Y, et al. Coffee polyphenols suppress diet-induced body fat accumulation by downregulating SREBP-1c and related molecules in C57BL/6J mice. American journal of physiology Endocrinology and metabolism. 2011;300(1):E122-33.## Abdollahi M, Marandi SM, Ghaedi K, Safaeinejad Z, Kazeminasab F, Shirkhani S, et al. Insulin-Related Liver Pathways and the Therapeutic Effects of Aerobic Training, Green Coffee, and Chlorogenic Acid Supplementation in Prediabetic Mice. Oxidative medicine and cellular longevity. 2022;2022:5318245.## Hamasaki H. Daily physical activity and type 2 diabetes: A review. World J Diabetes. 2016;7(12):243-51.##Seo DY, Park SH, Marquez J, Kwak H-B, Kim TN, Bae JH, et al. Hepatokines as a Molecular Transducer of Exercise. J Clin Med. 2021;10(3):385.## Li Y-P, Xiao J, Liang X, Pei Y, Han X-F, Li C-X, et al. DPP-4 inhibition resembles exercise in preventing type 2 diabetes development by inhibiting hepatic protein kinase C<sub>ε</sub> expression in a mouse model of hyperinsulinemia. J Int Med Res. 2020;48(6):300060520934635.##Zand A, Ibrahim K, Patham B. Prediabetes: Why Should We Care? Methodist DeBakey cardiovascular journal. 2018;14(4):289-97.## Stevanović J, Beleza J, Coxito P, Ascensão A, Magalhães J. Physical exercise and liver "fitness": Role of mitochondrial function and epigenetics-related mechanisms in non-alcoholic fatty liver disease. Molecular metabolism. 2020;32:1-14.##Abreu P, Vitzel KF, Monteiro IC, Lima TI, Queiroz AN, Leal-Cardoso JH, et al. Effects of endurance training on reduction of plasma glucose during high intensity constant and incremental speed tests in Wistar rats. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2016;49(11) e5226.## Dupuit M, Chavanelle V, Chassaing B, Perriere F, Etienne M, Plissonneau C, et al. The TOTUM-63 Supplement and High-Intensity Interval Training Combination Limits Weight Gain, Improves Glycemic Control, and Influences the Composition of Gut Mucosa-Associated Bacteria in Rats on a High Fat Diet. 2021;13(5):1569.## Wang Y, Xu D. Effects of aerobic exercise on lipids and lipoproteins. Lipids in health and disease. 2017;16(1):132.## Hayek T, Ito Y, Azrolan N, Verdery RB, Aalto-Setälä K, Walsh A, et al. Dietary fat increases high density lipoprotein (HDL) levels both by increasing the transport rates and decreasing the fractional catabolic rates of HDL cholesterol ester and apolipoprotein (Apo) A-I. Presentation of a new animal model and mechanistic studies in human Apo A-I transgenic and control mice. The Journal of clinical investigation. 1993;91(4):1665-71.## Mann S, Beedie C, Jimenez A. Differential effects of aerobic exercise, resistance training and combined exercise modalities on cholesterol and the lipid profile: review, synthesis and recommendations. Sports medicine (Auckland, NZ). 2014;44(2):211-21##Cui B, Liu S, Lin X, Wang J, Li S, Wang Q, et al. Effects of Lycium barbarum aqueous and ethanol extracts on high-fat-diet induced oxidative stress in rat liver tissue. Molecules (Basel, Switzerland). 2011;16(11):9116-28.## Amernia B, Moosavy SH, Banookh F, Zoghi G. FIB-4, APRI, and AST/ALT ratio compared to FibroScan for the assessment of hepatic fibrosis in patients with non-alcoholic fatty liver disease in Bandar Abbas, Iran. BMC gastroenterology. 2021;21(1):453.## Pawlak M, Lefebvre P, Staels B. Molecular mechanism of PPARα action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease. Journal of hepatology. 2015;62(3):720-33.## Gavito AL, Bautista D, Suarez J, Badran S, Arco R, Pavón FJ, et al. Chronic IL-6 Administration Desensitizes IL-6 Response in Liver, Causes Hyperleptinemia and Aggravates Steatosis in Diet-Induced-Obese Mice. PloS one. 2016;11(6):e0157956.## Guimaraes JC, Rocha M, Arkin AP. Transcript level and sequence determinants of protein abundance and noise in Escherichia coli. Nucleic acids research. 2014;42(8):4791-9##Greenbaum D, Colangelo C, Williams K, Gerstein M. Greenbaum D, Colangelo C, Williams K, Gerstein M. Comparing protein abundance and mRNA expression levels on a genomic scale. Genome Biol 4: 117. Genome biology. 2003;4:117.## Alves-Bezerra M, Cohen DE. Triglyceride Metabolism in the Liver. Comprehensive Physiology. 2017;8(1):1-8##