The Response of Some Hepatokines and Insulin Resistance to High Intensity Interval Training In Women with Non-Alcoholic Fatty Liver

Document Type : Research Paper

Authors

1 Department of Exercise Physiology, Faculty of Education and Psychology, Azarbaijan Shahid Madani University, Tabriz, Iran

2 Department of Exercise Physiology, Faculty of Sport Sciences, Urmia University, Urmia, Iran

Abstract

Background and Purpose: Liver hepatokines are one of the contributing factors in non-alcoholic fatty liver disease. One of the most effective treatments for this condition is exercise. Therefore, the aim of this study was to investigate the response of some liver hepatokines to a period of high intensity interval training in women with fatty liver.
Methodology: twenty Five women with non-alcoholic fatty liverwere randomly divided into two groups: exercise or control. The high intensity interval training protocol was performed for 8 weeks and four sessions per week for 60 minutes each session. Blood samples were taken from the arm vein to 5 cc pre- and post-test conditions. Plasma levels of Leukocyte-derived chemotaxin 2 (LECT2), angiopoietin-dependent growth factor (AGF), sex hormone-binding globulin (SHBG), and insulin were measured. Independent paired T-test was used to determine the intra-group changes of pre-test with post-test of dependent variables, and independent t-test was used to determine the significant difference between the groups.
Results: The present study showed that after eight weeks of intense interval training LECT2 and AGF in the training group compared to the control had a significant decrease and SHBG significantly increased (p <0.05). Also, insulin resistance, body fat percentage, body mass index and waist to pelvic hip ratio have been significantly reduced in the exercise group compared to the control group (p <0.05).
Conclusion: High intensity interval training in women seems to be a non-pharmacological solution to improve insulin resistance and improve fatty liver-related hepatokines.

Keywords


##Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. (2016)؛ Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.  J Hepatology، 64:73–84. doi: 10.1002/hep.28431.##Ekelund U, Steene-Johannessen J, Brown WJ, Fagerland MW, Owen N, Powell KE, et al. (2016)؛Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised metaanalysis of data from more than 1 million men and women. Lancet. Lancet. 24;388(10051):e6. doi: 10.1016/S0140-6736(16)31677-4.##Kerr J, Anderson C, Lippman SM. (2017)؛ Physical activity, sedentary behaviour, diet, and cancer: an update and emerging new evidence. Lancet Oncol. 18:457–471. doi: 10.1016/S1470-2045(17)30411-4.##Berube D, Seralini GE, Gagne R, Hammond GL.(1990)؛ Localization of the Human Sex Hormone-Binding Globulin Gene (Shbg) to the Short Arm of Chromosome-17 (17p12-p13). Cytogenet Cell Genet;54:65–7.##Perry JRB, Weedon MN, Langenberg C, Jackson AU, Lyssenko V, Sparso T, et al. (2010) ؛Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2 diabetes. Hum Mol Genet،19:535–44.##Lazo M, Zeb I, Nasir K, Tracy RP, Budoff MJ, Ouyang P, et al.(2015)؛ Association Between Endogenous Sex Hormones and Liver Fat in a Multiethnic Study of Atherosclerosis. Clin Gastroenterol Hepatol،13:1686–93.##Luo J, Chen Q, Shen T, Wang X, Fang W, Wu X, et al.(2018)؛ Association of sex hormone-binding globulin with nonalcoholic fatty liver disease in Chinese adults. Nutr Metab (Lond);15:79.##Hua X, Li M, Pan F, Xiao Y, Cui W, Hu Y.(2017)؛ Non-alcoholic fatty liver disease is an influencing factor for the association of SHBG with metabolic syndrome in diabetes patients. Sci Rep;7:14532.##Polyzos SA, Kountouras J, Tsatsoulis A, Zafeiriadou E, Katsiki E, Patsiaoura K, et al.(2013)؛ Sex steroids and sex hormone-binding globulin in postmenopausal women with nonalcoholic fatty liver disease. Hormones (Athens);12:405–16.##Hua X, Sun Y, Zhong Y, Feng W, Huang H, Wang W, et al. (2014)؛ Low serum sex hormone-binding globulin is associated with nonalcoholic fatty liver disease in type 2 diabetic patients. Clin Endocrinol (Oxf);80:877–83.##Oike Y, Yasunaga K, Ito Y, Matsumoto S, Maekawa H, Morisada T, et al. (2003)؛ Angiopoietin-related growth factor (AGF) promotes epidermal proliferation, remodeling, and regeneration. Proc Natl Acad Sci U S A;100:9494–9.##Ebert T, Kralisch S, Loessner U, Jessnitzer B, Stumvoll M, Fasshauer M, et al. (2014)؛ Relationship Between Serum Levels of Angiopoietin-Related Growth Factor and Metabolic Risk Factors. Horm Metab Res;46:685–90.##Ebert T, Bachmann A, Loessner U, Kratzsch J, Blueher M, Stumvoll M, et al. (2009)؛Serum levels of angiopoietin-related growth factor in diabetes mellitus and chronic hemodialysis. Metabolism;58:547–51.##Namkung J, Koh SB, Kong ID, Choi JW, Yeh BI. (2011)؛ Serum levels of angiopoietin- related growth factor are increased in metabolic syndrome. Metabolism;60:564–8.##Kitazawa M, Ohizumi Y, Oike Y, Hishinuma T, Hashimoto S. 2007؛ Angiopoietin- related growth factor suppresses gluconeogenesis through the akt/ forkhead box class O1-Dependent pathway in Hepatocytes. J Pharmacol Exp Ther;323:787–93.##Yamagoe S, Yamakawa Y, Matsuo Y, Minowada J, Mizuno S, Suzuki K .1996؛ Purification and primary amino acid sequence of a novel neutrophil chemotactic factor LECT2. Immunol Lett 52: 9–13. http://dx.doi.org/10.1016/0165-2478(96)02572-2.##Lan F, Misu H, Chikamoto K, Takayama H, Kikuchi A, Mohri K, Takata N, Hayashi H, Mutsazawa-Nagata N, Takeshita Y, Noda H, Matsumoto Y, Ota T, nagano T, Nakagen M, Miayamoto K, Takatsuki K, Seo T, Iwayama K, Tokuyama K, Matsugo S, Tang H, Saito Y, Yamoagoe S, Kaneko S, Takamura T؛ (2014) LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resitance. Diabetes 63: 1649–1664. http://dx.doi.org/10.2337/db13-0728.##Okumura A, Unoki-Kubota H, Matsushita Y, Shiga T, Moriyoshi Y, Yamagoe S, Kaburagi Y. 2013؛ Increased serum leukocyte cell-derived chemotaxin 2 (LECT2) in obesity and fatty liver. Biosci Trends7: 276–283. http://dx.doi.org/10.5582/bst.2013.v7.6.276.##Keating SE, Hackett DA, George J, Johnson NA. 2012؛ Exercise and non-alcoholic fatty liver disease: a systematic review and meta-analysis. Journal of hepatology. 57(1):157-66.##Dasgupta S, Bhattacharya S, Biswas A, Majumdar SS, Mukhopadhyay S, Ray S, Bhatta-Charya S .2010؛ NF-kB mediates lipid-induced fetuin- A expression in hepatocytes that impaires adipocyte function effecting insulin resistance. Biochem J 429: 451–462. http://dx.doi. org/10.1042/BJ20100330.##Elliott BT, Herbert P, Sculthorpe N, Grace FM, Stratton D, Hayes LD, Elliott CBT. 2017؛ Lifelong  exercise, but not short‐term high‐intensity interval training, increases GDF11, a marker of successful aging: a preliminary investigation. Physiol Rep.##Fletcher JA, Linden MA, Sheldon RD, Meers GM, Morris EM, Butterfield A, Perfield JW, Thyfault JP, Rector RS. 2016؛ Fibroblast growth factor 21 and exercise‐induced hepatic mitochondrial adaptations. Am J Physiol Gastrointest Liver Physiol 310: G832‐43.##Francois ME, Little JP. 2015؛ Effectiveness and safety of high‐intensity interval training in patients 708 with type 2 diabetes. Diabetes Spectr. 28: 39–44,.##Hackney AC, Lane AR. (2015)Exercise and the Regulation of Endocrine 733 Hormones. In: Progress in  molecular biology and translational science. 293–311.##Hayashino Y, Jackson JL, Hirata T, Fukumori N, Nakamura F, Fukuhara S, Tsujii S, Ishii H. 2014؛ Effects of exercise on C‐reactive protein, inflammatory cytokine and adipokine in patients  with type 2 diabetes: A meta‐analysis of randomized controlled trials. Metabolism 63: 431–440,.##Peter A, Kantartzis K, Machann J, Schick F, Staiger H, Machicao F, et al. (2010)؛  Relationships of circulating sex hormone-binding globulin with metabolic traits in humans. Diabetes 59:3167–73. doi: 10.2337/db10-0179.##Bonnet F, Velayoudom Cephise FL, Gautier A, Dubois S,Massart C, Camara A, et al. (2013) ؛ Role of sex steroids, intrahepatic fat and liver enzymes in the association between SHBG and metabolic features. Clin Endocrinol. 79:517–22. doi: 10.1111/cen.12089.##Kim JW, Kim DY. (2012)؛ Effects of aerobic exercise training on serum sex hormone binding globulin, body fat index, and metabolic syndrome factors in obese postmenopausal women. Metab Syndr Relat Disord. 10:452–7. doi: 10.1089/met.2012.0036.##Fahrner CL, Hackney AC. (1998)؛  Effects of endurance exercise on free testosterone concentration and the binding affinity of sex hormone binding globulin (SHBG). Int J Sports Med. 19:12–5. doi: 10.1055/s-2007-971872.##Tymchuk CN, Tessler SB, Barnard RJ. (2000)؛  Changes in sex hormone-binding globulin, insulin, and serum lipids in postmenopausal women on a lowfat, high-fiber diet combined with exercise. Nutr Cancer 38:158–62. doi: 10.1207/S15327914NC382_3.##Khorshidi D, Sarmadiyan M, Khoramjah M. (2016)؛ Effect of Aerobic- Strength Training on Sex Hormone Binding Globulin and Some Obesity Indices in Overweight and Obese Postmenopausal Women. ijbd. 9 (1) :14-20.##Monninkhof EM, Velthuis MJ, Peeters PH, Twisk JW, Schuit AJ.(2009)؛ Effect of exercise on postmenopausal sex hormone levels and role of body fat: a randomized controlled trial. J Clin Oncol . 27(27):4492-9.##McTiernan A, Tworoger SS, Ulrich CM, et al. (2004)؛Effect of exercise on serum estrogens in postmenopausal women: A 12-month randomized clinical trial. Cancer Res; 64:2923-8.##Friedenreich CM, Neilson HK, Woolcott CG, et al.(2011) Mediators and moderators of the effects of a year-long exercise intervention on endogenous sex hormones in postmenopausal women. Cancer Causes Control . 22:1365-73.##Plymate SR, Jones RE, Matej LA, Friedl KE.(1988)؛ Regulation of sex hormone binding globulin (SHBG) production in Hep G2 cells by insulin. Steroids . 52(4):339- 40.##McTiernan,Wu L, Chen C, Chlebowski R, Mossavar-Rahmani Y, Modungo F.(2006)؛ Relation of BMI and physical activity to sex hormones in postmenopausal women. Obesity;14(9):1662-77.##Simó R, Saez-Lopez C, Lecube A, Hernandez C, Fort JM, Selva DM. (2014)؛  Adiponectin upregulates SHBG production: molecular mechanisms and potential implications. Endocrinology 155:2820–30. doi: 10.1210/en.2014-1072.##Sreekumar R, Rosado B, Rasmussen D, CharltonM. (2003)؛  Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis. Hepatology. 38:244–51. doi: 10.1053/jhep.2003.50290.##Yamagoe S, Mizuno S, Suzuki K. (199؛  Molecular cloning of human and bovine LECT2 having a neutrophil chemotactic activity and its specific expression in the liver. Biochim Biophys Acta 1396:105–13. doi: 10.1016/S0167-4781(97)00181-4.##Sargeant JA, Aithal GP, Takamura T,Misu H, Takayama H, Douglas JA, et al. (2018)؛  The influence of adiposity and acute exercise on circulating hepatokines in normal weight and overweight/obese men. Appl Physiol Nutr Metab. 43:482–90. doi: 10.1139/apnm-2017-0639.##Inoue DS, De Mello MT, Foschini D, Lira FS, De Piano Ganen A, Da Silveria Campos RM, De Lima Sanches P, Silva PL, Corgosinho FC, Rossi FE, Tufik S, and Dâmaso AR. (2015)؛ Linear and undulating periodized strength plus aerobic training promote similar benefits and lead to improvement of insulin resistance on obese adolescents, Diabetes and its Complications. 29: 258-264.##Henriksen EJ. (2002)؛ Invited review: Effects of acute exercise and exercise training on insulin resistance, Journal of Applied Physiology. 93: 788-96.##Houmard JA, Hickey MS, Tyndall GL, Gavigan KE, Dohm G, Dohm L. (1995)؛Seven days of exercise increase GLUT-4 protein content in human skeletal muscle, Journal of Applied Physiology. 79:1936-1938.##Gilardini L, McTernan PG, Girola A, Da Silva NF, Alberti L, and Kumar S, et al. (2006)؛ Adiponectin is a candidate marker of metabolic syndrome in obese children and adolescents, Atherosclerosis. 189:401–407.##Wadden T, Stunkard A. 2004؛ Handbook of obesity treatment. New York: Guilford Press (1st Ed): 19.##Santos JM, Ribeiro SB, and Gaya AR. (2008)؛ Skeletal muscle pathways of contraction-enhanced glucose uptake. Journal of Sports Medicine, 29:785-94.##Ingerslev B, Hansen JS, Hoffmann C, Clemmesen JO, Secher NH, Scheler M, Hrabĕ de Angelis M, Häring HU, Pedersen BK, Weigert C, Plomgaard P. (2017)؛ Angiopoietin‐like protein 4 is an  exercise‐induced hepatokine in humans, regulated by glucagon and cAMP. Mol Metab. 6: 783 1286–1295.##Kong, In Deok; Kim, Min-Jeong; Kim, Dae Sik; Sim, Yun Bok; Kim, (2009)؛Na Hyun Habitual Exercise Decreases Serum Angiopoietin-related Growth Factor Levels In Healthy Human Subjects .Medicine & Science in Sports & Exercise:  41 (5): 494-495 .doi: 10.1249/01.MSS.0000356059.70642.b7.##Byung Il Yeh. Min-Jeong Kim. Jun Namkung. Jae-Seung Chang. (2018)؛ Downregulation Of Angptl6 Expression By Exercise In Mice And Human. Medicine & Science in Sports & Exercise 50:217-218 May with 11 Reads DOI: 10.1249/01.mss.0000535803.23025.8c.##