肝臟代謝失衡導致脂質異常堆積常在II型糖尿病症下觀察到，肝臟脂質的堆積會使肝細胞氧化壓力上升，並誘發發炎路徑IκB-α/NF-κB活化。過度活化發炎路徑會使體內促發炎細胞激素TNF-α與IL-6濃度上升，最終導致肝臟發炎與肝細胞損傷。長期運動訓練有助於改善肝臟的代謝壓力，減少肝臟脂質堆積並延緩糖尿病脂肪肝病的惡化。目前運動訓練調控能量代謝路徑影響IκB-α/NF-κB發炎訊號路徑的相互關聯仍尚未釐清，因此本研究目的在探討耐力運動訓練調控肝臟能量代謝路徑及發炎路徑對糖尿病小鼠肝臟功能的影響。方法：將16隻5週齡糖尿病db/db小鼠隨機分配到控制組與運動組。運動組進行8週的跑步訓練(跑步速度5.2 m/min，每次60分鐘，每週5次)，控制組不進行任何跑步訓練，於訓練結束後犧牲並取出肝臟，以西方墨點法(Western blot analyses)分析IκB-α/NF-κB發炎路徑與Sirt1/AMPK-α/PGC1-α能量代謝路徑蛋白表現、測量ALT、AST肝臟功能指標及肝臟組織病理切片觀察。結果：組織病理切片結果顯示，8週的耐力運動訓練後，糖尿病db/db小鼠肝臟脂質脂質空泡明顯減少。Sirt1/AMPK-α/PGC1-α蛋白活性顯著提高(P<0.05)，另外IκB-α/NF-κB蛋白磷酸化，則在運動訓練後也顯著提高(P<0.05)。然而肝功能的指標ALT與AST活性則在運動訓練後顯著下降(P<0.05)。結論：本研究結果證實耐力運動訓練有助於改善db/db小鼠肝臟能量代謝的失衡，達到減少肝臟脂質堆積的作用。

Hepatic lipid accumulation induced by metabolic dysfunction was accompanied with type II diabetes. Increased intrahepatic lipid content triggers oxidative stress, thus activating IκB-α/NF-κB pathway. Furthermore, activation of the inflammatory pathway and increases in circulating TNF-α and IL-6 levels cause liver damage. The purpose of this study was to determine whether exercise training upregulates the energy metabolism pathway and inhibits inflammatory pathway, thereby alleviating hepatic lipid accumulation and injury. Methods: Eight weeks moderate-intensity exercise (5m/min, 60min/day, and 5days/week for a total of 8weeks) on the Sirt1/AMPK-α/PGC1-α axis and NF-B pathway were investigated in liver of diabetic db/db (C57BL/KsJ-leprdb/leprdb) mice. The statistical significance of the differences between two groups was determined by independent sample t-test (P < 0.05). Results Upregulation of SIRT1 and PGC1-α expression and AMPK activity were observed in db/db mice with exercise training. Decreases in phosphorylation of IB and NF-B were observed in db/db mice with training compared with untrained mice. Conclusion Aerobic exercise training inhibits NFB signaling pathway and activates SIRT1/AMPK pathway, thereby alleviating hepatic lipid accumulation and injury.

國家實驗研究院. (2017). 「BKS.Cg-Dock7m +/+ Leprdb/J（db/db）糖尿病小鼠」. Retrieved from http://webserver.nlac.org.tw/n2/n2-2-1-20.asp

Abdul-Ghani, M. A., & DeFronzo, R. A. (2010). Pathogenesis of insulin resistance in skeletal muscle. BioMed Research International, 2010.

Aharoni-Simon, M., Hann-Obercyger, M., Pen, S., Madar, Z., & Tirosh, O. (2011). Fatty liver is associated with impaired activity of PPARγ-coactivator 1α (PGC1α) and mitochondrial biogenesis in mice. Laboratory Investigation, 91(7), 1018.

Ajmo, J. M., Liang, X., Rogers, C. Q., Pennock, B., & You, M. (2008). Resveratrol alleviates alcoholic fatty liver in mice. American Journal of Physiology-Gastrointestinal and Liver Physiology, 295(4), G833-G842.

Al-Rasadi, K., Rizzo, M., Montalto, G., & Berg, G. (2015). Nonalcoholic fatty liver disease, cardiovascular risk, and carotid inflammation: SAGE Publications Sage CA: Los Angeles, CA.

Asghar, M., George, L., & Lokhandwala, M. F. (2007). Exercise decreases oxidative stress and inflammation and restores renal dopamine D1 receptor function in old rats. American Journal of Physiology-Renal Physiology, 293(3), F914-F919.

Aslam, M., Aggarwal, S., Sharma, K. K., Galav, V., & Madhu, S. V. (2016). Postprandial hypertriglyceridemia predicts development of insulin resistance glucose intolerance and type 2 diabetes. PloS one, 11(1), e0145730.

Barcelos, R. P., Bresciani, G., Rodriguez-Miguelez, P., Cuevas, M. J., Soares, F. A. A., Barbosa, N. V., & González-Gallego, J. (2016). Diclofenac pretreatment effects on the toll-like receptor 4/nuclear factor kappa B-mediated inflammatory response to eccentric exercise in rat liver. Life sciences, 148, 247-253.

Barker, D. J., Hales, C. N., Fall, C., Osmond, C., Phipps, K., & Clark, P. (1993). Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia, 36(1), 62-67.

Batatinha, H. A., Lima, E. A., Teixeira, A. A., Souza, C. O., Biondo, L. A., Silveira, L. S., . . . Rosa Neto, J. C. (2017). Association Between Aerobic Exercise and Rosiglitazone Avoided the NAFLD and Liver Inflammation Exacerbated in PPAR‐α Knockout Mice. Journal of cellular physiology, 232(5), 1008-1019.

Begriche, K., Massart, J., Robin, M. A., Bonnet, F., & Fromenty, B. (2013). Mitochondrial adaptations and dysfunctions in nonalcoholic fatty liver disease. Hepatology, 58(4), 1497-1507.

Boden, G. (2006). Fatty acid—induced inflammation and insulin resistance in skeletal muscle and liver. Current diabetes reports, 6(3), 177-181.

Boden, G. (2008). Obesity and free fatty acids. Endocrinology and metabolism clinics of North America, 37(3), 635-646.

Boden, G., She, P., Mozzoli, M., Cheung, P., Gumireddy, K., Reddy, P., . . . Ruderman, N. (2005). Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-κB pathway in rat liver. Diabetes, 54(12), 3458-3465.

Botta, A., Laher, I., Beam, J., DeCoffe, D., Brown, K., Halder, S., . . . Ghosh, S. (2013). Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts. PloS one, 8(8), e70248.

Braidy, N., Guillemin, G. J., Mansour, H., Chan-Ling, T., Poljak, A., & Grant, R. (2011). Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. PloS one, 6(4), e19194.

Browning, J. D., & Horton, J. D. (2004). Molecular mediators of hepatic steatosis and liver injury. Journal of Clinical Investigation, 114(2), 147.

Buzzetti, E., Pinzani, M., & Tsochatzis, E. A. (2016). The multiple-hit pathogenesis of non-alcoholic fatty liver disease (NAFLD). Metabolism, 65(8), 1038-1048.

Cahill, G. F., Ashmore, J., Renold, A. E., & Hastings, A. B. (1959). Blood glucose and the liver. The American journal of medicine, 26(2), 264-282.

Cantó, C., & Auwerx, J. (2009). PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Current opinion in lipidology, 20(2), 98.

Chen, S., Zhao, X., Ran, L., Wan, J., Wang, X., Qin, Y., . . . Zhang, Q. (2015). Resveratrol improves insulin resistance, glucose and lipid metabolism in patients with non-alcoholic fatty liver disease: a randomized controlled trial. Digestive and Liver Disease, 47(3), 226-232.

Chen, W., Lin, Y.-J., Zhou, X.-Y., Chen, H., & Jin, Y. (2015). Rosiglitazone protects rat liver against acute liver injury associated with the NF-κB signaling pathway. Canadian journal of physiology and pharmacology, 94(1), 28-34.

Circu, M. L., & Aw, T. Y. (2010). Reactive oxygen species, cellular redox systems, and apoptosis. Free Radical Biology and Medicine, 48(6), 749-762.

Clark, J. M. (2006). The epidemiology of nonalcoholic fatty liver disease in adults. Journal of clinical gastroenterology, 40, S5-S10.

Clinic., M. (2015). Liver function tests Retrieved from https://www.mayoclinic.org/tests-procedures/liver-function-tests/basics/results/prc-20012602

Cohen, J. C., Horton, J. D., & Hobbs, H. H. (2011). Human fatty liver disease: old questions and new insights. Science, 332(6037), 1519-1523.

Cool, B., Zinker, B., Chiou, W., Kifle, L., Cao, N., Perham, M., . . . Iyengar, R. (2006). Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell metabolism, 3(6), 403-416.

Costill, D., Coyle, E., Dalsky, G., Evans, W., Fink, W., & Hoopes, D. (1977). Effects of elevated plasma FFA and insulin on muscle glycogen usage during exercise. Journal of applied physiology, 43(4), 695-699.

Dandona, P., Aljada, A., & Bandyopadhyay, A. (2004). Inflammation: the link between insulin resistance, obesity and diabetes. Trends in immunology, 25(1), 4-7.

de Castro, C. A., Natali, A. J., Cardoso, L. M., Ferreira-Machado, A. B., Novello, A. A., da Silva, K. A., . . . Peluzio, M. d. C. G. (2014). Aerobic exercise and not a diet supplemented with jussara açaí (Euterpe edulis Martius) alters hepatic oxidative and inflammatory biomarkers in ApoE-deficient mice. British Journal of Nutrition, 112(3), 285-294.

DeFronzo, R. (2010). Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia, 53(7), 1270-1287.

Deng, X. Q., Chen, L. L., & Li, N. X. (2007). The expression of SIRT1 in nonalcoholic fatty liver disease induced by high‐fat diet in rats. Liver International, 27(5), 708-715.

Diano, S., & Horvath, T. L. (2012). Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism. Trends in molecular medicine, 18(1), 52-58.

Ding, R.-B., Bao, J., & Deng, C.-X. (2017). Emerging roles of SIRT1 in fatty liver diseases. International journal of biological sciences, 13(7), 852.

Eguchi, Y., Mizuta, T., Sumida, Y., Ishibashi, E., Kitajima, Y., Isoda, H., . . . Takahashi, H. (2011). The pathological role of visceral fat accumulation in steatosis, inflammation, and progression of nonalcoholic fatty liver disease. Journal of gastroenterology, 46(1), 70-78.

El-Kader, S. A., Gari, A., & El-Den, A. S. (2013). Impact of moderate versus mild aerobic exercise training on inflammatory cytokines in obese type 2 diabetic patients: a randomized clinical trial. African health sciences, 13(4), 857-863.

Eo, H., Jeon, Y.-j., Lee, M., & Lim, Y. (2014). Brown Alga Ecklonia cava polyphenol extract ameliorates hepatic lipogenesis, oxidative stress, and inflammation by activation of AMPK and SIRT1 in high-fat diet-induced obese mice. Journal of agricultural and food chemistry, 63(1), 349-359.

Evans, J. L., Goldfine, I. D., Maddux, B. A., & Grodsky, G. M. (2002). Oxidative stress and stress-activated signaling pathways: a unifying hypothesis of type 2 diabetes. Endocrine reviews, 23(5), 599-622.

Fabbrini, E., Sullivan, S., & Klein, S. (2010). Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology, 51(2), 679-689.

Fenster, C. P., Weinsier, R. L., Darley‐Usmar, V. M., & Patel, R. P. (2002). Obesity, aerobic exercise, and vascular disease: the role of oxidant stress. Obesity, 10(9), 964-968.

Fu, J.-H., Sun, H.-S., Wang, Y., Zheng, W.-Q., Shi, Z.-Y., & Wang, Q.-J. (2010). The effects of a fat-and sugar-enriched diet and chronic stress on nonalcoholic fatty liver disease in male Wistar rats. Digestive diseases and sciences, 55(8), 2227-2236.

Fu, Y., Luo, N., Klein, R. L., & Garvey, W. T. (2005). Adiponectin promotes adipocyte differentiation, insulin sensitivity, and lipid accumulation. Journal of lipid research, 46(7), 1369-1379.

Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., . . . Shimomura, I. (2017). Increased oxidative stress in obesity and its impact on metabolic syndrome. The Journal of clinical investigation, 114(12), 1752-1761.

Galloway, C. A., Lee, H., Brookes, P. S., & Yoon, Y. (2014). Decreasing mitochondrial fission alleviates hepatic steatosis in a murine model of nonalcoholic fatty liver disease. American Journal of Physiology-Gastrointestinal and Liver Physiology, 307(6), G632-G641.

Ghosh, S., Khazaei, M., Moien-Afshari, F., Ang, L. S., Granville, D. J., Verchere, C., . . . Sharma, K. (2009). Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease in db/db mice. American Journal of Physiology-Renal Physiology, 296(4), F700-F708.

Hales, C. N., & Barker, D. J. (1992). Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia, 35(7), 595-601.

Hameed, I., Masoodi, S. R., Mir, S. A., Nabi, M., Ghazanfar, K., & Ganai, B. A. (2015). Type 2 diabetes mellitus: from a metabolic disorder to an inflammatory condition. World journal of diabetes, 6(4), 598.

Hannon, T. S., Rao, G., & Arslanian, S. A. (2005). Childhood obesity and type 2 diabetes mellitus. Pediatrics, 116(2), 473-480.

Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012). AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nature reviews Molecular cell biology, 13(4), 251.

Haus, J. M., Solomon, T. P., Kelly, K. R., Fealy, C. E., Kullman, E. L., Scelsi, A. R., . . . Flask, C. A. (2013). Improved hepatic lipid composition following short-term exercise in nonalcoholic fatty liver disease. The Journal of Clinical Endocrinology & Metabolism, 98(7), E1181-E1188.

Hsu, W.-H., Chen, T.-H., Lee, B.-H., Hsu, Y.-W., & Pan, T.-M. (2014). Monascin and ankaflavin act as natural AMPK activators with PPARα agonist activity to down-regulate nonalcoholic steatohepatitis in high-fat diet-fed C57BL/6 mice. Food and chemical toxicology, 64, 94-103.

Hu, F. B., Manson, J. E., Stampfer, M. J., Colditz, G., Liu, S., Solomon, C. G., & Willett, W. C. (2001). Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. New England Journal of Medicine, 345(11), 790-797.

Huang, C.-C., Tsai, S.-C., & Lin, W.-T. (2008). Potential ergogenic effects of L-arginine against oxidative and inflammatory stress induced by acute exercise in aging rats. Experimental gerontology, 43(6), 571-577.

Ipekci, S. H., Basaranoglu, M., & Sonsuz, A. (2003). The fluctuation of serum levels of aminotransferase in patients with nonalcoholic steatohepatitis. Journal of clinical gastroenterology, 36(4), 371.

Iwabu, M., Yamauchi, T., Okada-Iwabu, M., Sato, K., Nakagawa, T., Funata, M., . . . Tabata, M. (2010). Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca 2+ and AMPK/SIRT1. Nature, 464(7293), 1313.

Kawano, Y., & Cohen, D. E. (2013). Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease. Journal of gastroenterology, 48(4), 434-441.

Kleiner, D. E., Brunt, E. M., Van Natta, M., Behling, C., Contos, M. J., Cummings, O. W., . . . Unalp‐Arida, A. (2005). Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology, 41(6), 1313-1321.

Kokoszka, J. E., Coskun, P., Esposito, L. A., & Wallace, D. C. (2001). Increased mitochondrial oxidative stress in the Sod2 (+/−) mouse results in the age-related decline of mitochondrial function culminating in increased apoptosis. Proceedings of the National Academy of Sciences, 98(5), 2278-2283.

Koya, S., Kawaguchi, T., Hashida, R., Goto, E., Matsuse, H., Saito, H., . . . Imanaga, M. (2017). Effects of in‐hospital exercise on liver function, physical ability, and muscle mass during treatment of hepatoma in patients with chronic liver disease. Hepatology Research, 47(3).

Lee, J., Hong, S.-W., Rhee, E.-J., & Lee, W.-Y. (2012). GLP-1 receptor agonist and non-alcoholic fatty liver disease. Diabetes & metabolism journal, 36(4), 262-267.

Li, L., Mühlfeld, C., Niemann, B., Pan, R., Li, R., Hilfiker-Kleiner, D., . . . Rohrbach, S. (2011). Mitochondrial biogenesis and PGC-1α deacetylation by chronic treadmill exercise: differential response in cardiac and skeletal muscle. Basic research in cardiology, 106(6), 1221-1234.

Linden, M. A., Sheldon, R. D., Meers, G. M., Ortinau, L. C., Morris, E. M., Booth, F. W., . . . Ibdah, J. A. (2016). Aerobic exercise training in the treatment of non‐alcoholic fatty liver disease related fibrosis. The Journal of physiology, 594(18), 5271-5284.

Lira, F. S., Koyama, C. H., Yamashita, A. S., Rosa, J. C., Zanchi, N. E., Batista, M. L., & Seelaender, M. C. (2009). Chronic exercise decreases cytokine production in healthy rat skeletal muscle. Cell biochemistry and function, 27(7), 458-461.

Makris, K. C., Andrianou, X. D., Charisiadis, P., Burch, J. B., Seth, R. K., Ioannou, A., . . . Chatterjee, S. (2016). Association between exposures to brominated trihalomethanes, hepatic injury and type II diabetes mellitus. Environment international, 92, 486-493.

Mantena, S. K., King, A. L., Andringa, K. K., Eccleston, H. B., & Bailey, S. M. (2008). Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol-and obesity-induced fatty liver diseases. Free Radical Biology and Medicine, 44(7), 1259-1272.

McPherson, S., Stewart, S. F., Henderson, E., Burt, A. D., & Day, C. P. (2010). Simple non-invasive fibrosis scoring systems can reliably exclude advanced fibrosis in patients with non-alcoholic fatty liver disease. Gut, 59(9), 1265-1269.

Mehmood, T., Maryam, A., Tian, X., Khan, M., & Ma, T. (2017). Santamarine Inhibits NF-кB and STAT3 Activation and Induces Apoptosis in HepG2 Liver Cancer Cells via Oxidative Stress. Journal of Cancer, 8(18), 3707.

Mehta, K., Van Thiel, D. H., Shah, N., & Mobarhan, S. (2002). Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. Nutrition reviews, 60(9), 289-293.

Moghaddam, D. A., Heber, A., Capin, D., Kreutz, T., Opitz, D., Lenzen, E., . . . Brinkmann, C. (2011). Training increases peroxiredoxin 2 contents in the erythrocytes of overweight/obese men suffering from type 2 diabetes. WMW Wiener Medizinische Wochenschrift, 161(21), 511-518.

Musso, G., Cassader, M., Rosina, F., & Gambino, R. (2012). Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials. Diabetologia, 55(4), 885-904.

Muthusamy, V. R., Kannan, S., Sadhaasivam, K., Gounder, S. S., Davidson, C. J., Boeheme, C., . . . Rajasekaran, N. S. (2012). Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. Free Radical Biology and Medicine, 52(2), 366-376.

Nikroo, H., Nematy, M., Sima, H., AttarzadeHosseini, S., Pezeshki, M., Esmaeilzadeh, A., . . . MohammadianDamasaki, M. (2013). Therapeutic effects of aerobic exercise and low-calorie diet on nonalcoholic steatohepatitis. Govaresh, 17(4), 245-253.

Oh, S., So, R., Shida, T., Matsuo, T., Kim, B., Akiyama, K., . . . Shoda, J. (2017). High-intensity aerobic exercise improves both hepatic fat content and stiffness in sedentary obese men with nonalcoholic fatty liver disease. Scientific reports, 7, 43029.

Oliveira, V. N. d., Bessa, A., Jorge, M. L. M. P., Oliveira, R. J. d. S., de Mello, M. T., De Agostini, G. G., . . . Espindola, F. S. (2012). The effect of different training programs on antioxidant status, oxidative stress, and metabolic control in type 2 diabetes. Applied Physiology, Nutrition, and Metabolism, 37(2), 334-344.

Ong, J. P., Elariny, H., Collantes, R., Younoszai, A., Chandhoke, V., Reines, H. D., . . . Younossi, Z. M. (2005). Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obesity surgery, 15(3), 310-315.

Orhan, C., Akdemir, F., Sahin, N., Tuzcu, M., Komorowski, J., Hayirli, A., & Sahin, K. (2012). Chromium histidinate protects against heat stress by modulating the expression of hepatic nuclear transcription factors in quail. British poultry science, 53(6), 828-835.

Ott, M., Gogvadze, V., Orrenius, S., & Zhivotovsky, B. (2007). Mitochondria, oxidative stress and cell death. Apoptosis, 12(5), 913-922.

Pala, R., Orhan, C., Tuzcu, M., Sahin, N., Ali, S., Cinar, V., . . . Sahin, K. (2016). Coenzyme Q10 supplementation modulates NFκB and Nrf2 pathways in exercise training. Journal of sports science & medicine, 15(1), 196.

Pan, J. H., Lim, Y., Kim, J. H., Heo, W., Lee, K. Y., Shin, H. J., . . . Kim, Y. J. (2017). Root bark of Ulmus davidiana var. japonica restrains acute alcohol-induced hepatic steatosis onset in mice by inhibiting ROS accumulation. PloS one, 12(11), e0188381.

Parrott, C. R., Ghosh, P., Tedeschi, J., Gunasekara, G., & Broderick, T. L. (2011). Urinary corticosterone and normetanephrine levels after voluntary wheel and forced treadmill running in the db/db mouse. J Diabetes Mellitus, 1(4), 71-78.

Pasarín, M., La Mura, V., Gracia-Sancho, J., García-Calderó, H., Rodríguez-Vilarrupla, A., García-Pagán, J. C., . . . Abraldes, J. G. (2012). Sinusoidal endothelial dysfunction precedes inflammation and fibrosis in a model of NAFLD. PloS one, 7(4), e32785.

Perry, R. J., Camporez, J. P. G., Kursawe, R., Titchenell, P. M., Zhang, D., Perry, C. J., ... & Ruan, H. B. (2015). Hepatic acetyl CoA links adipose tissue inflammation to hepatic insulin resistance and type 2 diabetes.Cell,160(4), 745-758.

Pessayre, D. (2007). Role of mitochondria in non‐alcoholic fatty liver disease. Journal of gastroenterology and hepatology, 22(s1).

Petersen, A. M. W., & Pedersen, B. K. (2005). The anti-inflammatory effect of exercise. Journal of applied physiology, 98(4), 1154-1162.

Pinto, P. R., Rocco, D. D. F. M., Okuda, L. S., Machado-Lima, A., Castilho, G., da Silva, K. S., . . . da Silva Ferreira, G. (2015). Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta. Lipids in health and disease, 14(1), 109.

Radák, Z., Chung, H. Y., Naito, H., Takahashi, R., Jung, K. J., Kim, H.-J., & Goto, S. (2004). Age-associated increase in oxidative stress and nuclear factor κB activation are attenuated in rat liver by regular exercise. The FASEB journal, 18(6), 749-750.

Rinella, M. E., & Green, R. M. (2004). The methionine-choline deficient dietary model of steatohepatitis does not exhibit insulin resistance. Journal of hepatology, 40(1), 47-51.

Roberts, C. K., & Sindhu, K. K. (2009). Oxidative stress and metabolic syndrome. Life sciences, 84(21), 705-712.

Sallam, N., Khazaei, M., & Laher, I. (2010). Effect of moderate-intensity exercise on plasma C-reactive protein and aortic endothelial function in type 2 diabetic mice. Mediators of inflammation, 2010.

Samuel, V. T., Petersen, K. F., & Shulman, G. I. (2010). Lipid-induced insulin resistance: unravelling the mechanism. The Lancet, 375(9733), 2267-2277.

Satapati, S., Kucejova, B., Duarte, J. A., Fletcher, J. A., Reynolds, L., Sunny, N. E., ... & Merritt, M. E. (2015). Mitochondrial metabolism mediates oxidative stress and inflammation in fatty liver. The Journal of clinical investigation,125(12), 4447-4462.

Sathyanarayana, P., Jogi, M., Muthupillai, R., Krishnamurthy, R., Samson, S. L., & Bajaj, M. (2011). Effects of combined exenatide and pioglitazone therapy on hepatic fat content in type 2 diabetes. Obesity, 19(12), 2310-2315.

Savage, D. B., Petersen, K. F., & Shulman, G. I. (2007). Disordered lipid metabolism and the pathogenesis of insulin resistance. Physiological reviews, 87(2), 507-520.

Sennott, J., Morrissey, J., Standley, P. R., & Broderick, T. L. (2008). Treadmill exercise training fails to reverse defects in glucose, insulin and muscle GLUT4 content in the db/db mouse model of diabetes. Pathophysiology, 15(3), 173-179.

Shoelson, S., Lee, J., & Yuan, M. (2003). Inflammation and the IKKβ/IκB/NF-κB axis in obesity-and diet-induced insulin resistance. International journal of obesity, 27(S3), S49.

Sies, H. (1997). Oxidative stress: oxidants and antioxidants. Experimental physiology, 82(2), 291-295.

Sims, N. R., & Muyderman, H. (2010). Mitochondria, oxidative metabolism and cell death in stroke. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 1802(1), 80-91.
Srinivasan, K., & Ramarao, P. (2007). Animal models in type 2 diabetes research: an overview. Indian Journal of Medical Research, 125(3), 451.

Tak, P. P., & Firestein, G. S. (2001). NF-κB: a key role in inflammatory diseases. The Journal of clinical investigation, 107(1), 7-11.

Takamura, T., Misu, H., Ota, T., & Kaneko, S. (2012). Fatty liver as a consequence and cause of insulin resistance: lessons from type 2 diabetic liver. Endocrine journal, 59(9), 745-763.

Tang, Y., Li, J., Gao, C., Xu, Y., Li, Y., Yu, X., Wang, J., Liu, L. and Yao, P. (2016) Hepatoprotective effect of quercetin on endoplasmic reticulum stress and inflammation after intense exercise in mice through phosphoinositide 3-kinase and nuclear factor-kappa B. Oxidative medicine and cellular longevity,2016.

Teixeira-Lemos, E., Nunes, S., Teixeira, F., & Reis, F. (2011). Regular physical exercise training assists in preventing type 2 diabetes development: focus on its antioxidant and anti-inflammatory properties. Cardiovascular diabetology, 10(1), 12.

Teixeira de Lemos, E., Pinto, R., Oliveira, J., Garrido, P., Sereno, J., Mascarenhas-Melo, F., . . . Reis, F. (2011). Differential effects of acute (extenuating) and chronic (training) exercise on inflammation and oxidative stress status in an animal model of type 2 diabetes mellitus. Mediators of inflammation, 2011.

Than, N. N., & Newsome, P. N. (2015). A concise review of non-alcoholic fatty liver disease. Atherosclerosis, 239(1), 192-202.

Titchenell PM, Quinn WJ, Lu M, Chu Q, Lu W, Li C, Chen H, Monks BR, Chen J, Rabinowitz JD, Birnbaum MJ (2016) Direct hepatocyte insulin signaling is required for lipogenesis but is dispensable for the suppression of glucose production. Cell metabolism, 23(6), 1154-1166.

Touyz, R. M. (2004). Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension. Hypertension, 44(3), 248-252.

Tuomilehto, J., Lindström, J., Eriksson, J. G., Valle, T. T., Hämäläinen, H., Ilanne-Parikka, P., . . . Rastas, M. (2001). Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. New England Journal of Medicine, 344(18), 1343-1350.
Turrens, J. F. (2003). Mitochondrial formation of reactive oxygen species. The Journal of physiology, 552(2), 335-344.

Ucar, F., Sezer, S., Erdogan, S., Akyol, S., Armutcu, F., & Akyol, O. (2013). The relationship between oxidative stress and nonalcoholic fatty liver disease: Its effects on the development of nonalcoholic steatohepatitis. Redox Report, 18(4), 127-133.

Veneroso, C., Tuñón, M. J., González‐Gallego, J., & Collado, P. S. (2009). Melatonin reduces cardiac inflammatory injury induced by acute exercise. Journal of pineal research, 47(2), 184-191.

Wilson, P. W., D’Agostino, R. B., Parise, H., Sullivan, L., & Meigs, J. B. (2005). Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation, 112(20), 3066-3072.

Woo, S. L., Xu, H., Li, H., Zhao, Y., Hu, X., Zhao, J., ... & Pei, Y. (2014). Metformin ameliorates hepatic steatosis and inflammation without altering adipose phenotype in diet-induced obesity.PloS one,9(3), e91111.

Xiao, H., Xie, G., Wang, J., Hou, X., Wang, X., Wu, W., & Liu, X. (2013). Chicoric acid prevents obesity by attenuating hepatic steatosis, inflammation and oxidative stress in high-fat diet-fed mice. Food research international, 54(1), 345-353.

Yamamoto, Y., & Gaynor, R. B. (2001). Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. The Journal of clinical investigation, 107(2), 135-142.

Yano, E., Tagawa, K., Yamaoka, K., & Mori, M. (2001). Test validity of periodic liver function tests in a population of Japanese male bank employees. Journal of clinical epidemiology, 54(9), 945-951.

Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004). Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase. The EMBO journal, 23(12), 2369-2380.

Yoshimura, E., Kumahara, H., Tobina, T., Ayabe, M., Matono, S., Anzai, K., . . . Tanaka, H. (2011). A 12-week aerobic exercise program without energy restriction improves intrahepatic fat, liver function and atherosclerosis-related factors. Obesity research & clinical practice, 5(3), e249-e257.

Zhang, X., Li, Z. Z., Liu, D. F., Xu, X., Mei, Z. C., & Shen, W. (2009). ANGIOTENSIN‐CONVERTING ENZYME INHIBITORS IMPROVE HEPATIC STEATOSIS BY MODULATING EXPRESSION OF TUMOUR NECROSIS FACTOR‐α, INTERLEUKIN‐6 AND ADIPONECTIN RECEPTOR‐2 IN RATS WITH TYPE 2 DIABETES. Clinical and Experimental Pharmacology and Physiology, 36(7), 631-636.

Zulet, M. A., Barber, A., Garcin, H., Higueret, P., & Martinez, J. A. (1999). Alterations in carbohydrate and lipid metabolism induced by a diet rich in coconut oil and cholesterol in a rat model. Journal of the American College of Nutrition, 18(1), 36-42.