Does physical inactivity cause nonalcoholic fatty liver disease?

Journal of Applied Physiology

Volumn 111, Issue 6, 2011, Pages 1828-1835

  Rector, R Scott ^a,b,c   Thyfault, John P ^a,b,c  

^a Division of Gastroenterology and Hepatology   (United States)

^b University of Missouri   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Aerobic fitness; Insulin resistance; Overnutrition

Indexed keywords

CROSS-SECTIONAL STUDY; EXERCISE; FATTY LIVER; FITNESS; HUMAN; KINESIOTHERAPY; OVERNUTRITION; PATHOPHYSIOLOGY; PUBLIC HEALTH; REVIEW; RISK FACTOR; SEDENTARY LIFESTYLE;

CROSS-SECTIONAL STUDIES; EXERCISE; EXERCISE THERAPY; FATTY LIVER; HUMANS; OVERNUTRITION; PHYSICAL FITNESS; PUBLIC HEALTH; RISK FACTORS; SEDENTARY LIFESTYLE;

EID: 80054687396     PISSN: 87507587     EISSN: 15221601     Source Type: Journal    
DOI: 10.1152/japplphysiol.00384.2011     Document Type: Review

References (93)

1. Alibegovic AC, Hojbjerre L, Sonne MP, van Hall G, Stallknecht B, Dela F, Vaag A. Impact of 9 days of bed rest on hepatic and peripheral insulin action, insulin secretion, and whole-body lipolysis in healthy young male offspring of patients with type 2 diabetes. Diabetes 58: 2749-2756, 2009.
2. Arrese M. Nonalcoholic fatty liver disease: liver disease: an overlooked complication of diabetes mellitus. Nat Rev Endocrinol 6: 660-661, 2010.
3. Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, Cristanini G, Tiribelli C. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 132: 112-117, 2000. (Pubitemid 30044177)
4. Berglund ED, Lee-Young RS, Lustig DG, Lynes SE, Donahue EP, Camacho RC, Meredith ME, Magnuson MA, Charron MJ, Wasserman DH. Hepatic energy state is regulated by glucagon receptor signaling in mice. J Clin Invest 119: 2412-2422, 2009.
5. Blair SN, Kohl HW 3rd, Barlow CE, Paffenbarger RS Jr, Gibbons LW, Macera CA. Changes in physical fitness and all-cause mortality A prospective study of healthy and unhealthy men. JAMA 273: 1093-1098, 1995.
6. Blair SN, Kohl HW 3rd Paffenbarger RS Jr, Clark DG, Cooper KH, Gibbons LW. Physical fitness and all-cause mortality A prospective study of healthy men and women. JAMA 262: 2395-2401, 1989. (Pubitemid 19261810)
7. Blanc S, Normand S, Pachiaudi C, Fortrat JO, Laville M, Gharib C. Fuel homeostasis during physical inactivity induced by bed rest. J Clin Endocrinol Metab 85: 2223-2233, 2000. (Pubitemid 32269247)
8. Booth FW, Chakravarthy MV, Gordon SE, Spangenburg EE. Waging war on physical inactivity: using modern molecular ammunition against an ancient enemy. J Appl Physiol 93: 3-30, 2002. (Pubitemid 34686188)
9. Booth FW, Chakravarthy MV, Spangenburg EE. Exercise and gene expression: physiological regulation of the human genome through physical activity. J Physiol 543: 399-411, 2002. (Pubitemid 35012197)
10. Booth FW, Laye MJ, Lees SJ, Rector RS, Thyfault JP. Reduced physical activity and risk of chronic disease: the biology behind the consequences. Eur J Appl Physiol 102: 381-390, 2008.
11. Bouchard C, Rankinen T. Individual differences in response to regular physical activity. Med Sci Sports Exerc 33: S446-S451; discussion S452-S443, 2001. (Pubitemid 32524736)
12. Brown MS, Goldstein JL. Selective versus total insulin resistance: a pathogenic paradox. Cell Metab 7: 95-96, 2008. (Pubitemid 351168559)
13. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest 114: 147-152, 2004. (Pubitemid 39071617)
14. Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, Grundy SM, Hobbs HH. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 40: 1387-1395, 2004. (Pubitemid 39657013)
15. Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 42: 987-1000, 2005. (Pubitemid 43112663)
16. Caldwell S, Lazo M. Is exercise an effective treatment for NASH? Knowns and unknowns. Ann Hepatol 8, Suppl 1: S60-S66, 2009.
17. Chakravarthy MV, Booth FW. Eating, exercise, and "thrifty" genotypes: connecting the dots toward an evolutionary understanding of modern chronic diseases. J Appl Physiol 96: 3-10, 2004. (Pubitemid 38035170)
18. Chiarelli F, Marcovecchio ML. Insulin resistance and obesity in childhood. Eur J Endocrinol 159, Suppl 1:S67-S74, 2008.
19. Church TS, Kuk JL, Ross R, Priest EL, Biltoft E, Blair SN. Association of cardiorespiratory fitness, body mass index, and waist circumference to nonalcoholic fatty liver disease. Gastroenterology 130: 2023-2030, 2006. (Pubitemid 43816951)
20. David K, Kowdley KV, Unalp A, Kanwal F, Brunt EM, Schwimmer JB. Quality of life in adults with nonalcoholic fatty liver disease: baseline data from the nonalcoholic steatohepatitis clinical research network. Hepatology 49: 1904-1912, 2009.
21. De Souza CT, Frederico MJ, da Luz G, Cintra DE, Ropelle ER, Pauli JR, Velloso LA. Acute exercise reduces hepatic glucose production through inhibition of the Foxo1/HNF-4alpha pathway in insulin resistant mice. J Physiol 588: 2239-2253, 2010.
22. Devries MC, Samjoo IA, Hamadeh MJ, Tarnopolsky MA. Effect of endurance exercise on hepatic lipid content, enzymes, and adiposity in men and women. Obesity (Silver Spring) 16: 2281-2288, 2008.
23. Dunn W, Xu R, Wingard DL, Rogers C, Angulo P, Younossi ZM, Schwimmer JB. Suspected nonalcoholic fatty liver disease and mortality risk in a population-based cohort study. Am J Gastroenterol 103: 2263-2271, 2008.
24. Ekelund U, Sardinha LB, Anderssen SA, Harro M, Franks PW, Brage S, Cooper AR, Andersen LB, Riddoch C, Froberg K. Associations between objectively assessed physical activity and indicators of body fatness in 9-to 10-y-old European children: a population-based study from 4 distinct regions in Europe (the European Youth Heart Study). Am J Clin Nutr 80: 584-590, 2004. (Pubitemid 41115521)
25. Estall JL, Kahn M, Cooper MP, Fisher FM, Wu MK, Laznik D, Qu L, Cohen DE, Shulman GI, Spiegelman BM. Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression. Diabetes 58: 1499-1508, 2009.
26. Franks PW, Ekelund U, Brage S, Wong MY, Wareham NJ. Does the association of habitual physical activity with the metabolic syndrome differ by level of cardiorespiratory fitness? Diabetes Care 27: 1187-1193, 2004. (Pubitemid 38579788)
27. Hannukainen JC, Borra R, Lindeborg K, Kallio H, Kiss J, Lepomaki V, Kalliokoski KK, Kujala UM, Kaprio J, Heinonen OJ, Komu M, Parkkola R, Ahotupa M, Lehtimaki T, Huupponen R, Iozzo P, Nuutila P. Liver and pancreatic fat content and metabolism in healthy monozygotic twins with discordant physical activity. J Hepatol 54: 545-552, 2011.
28. Hannukainen JC, Nuutila P, Ronald B, Kaprio J, Kujala UM, Janatuinen T, Heinonen OJ, Kapanen J, Viljanen T, Haaparanta M, Ronnemaa T, Parkkola R, Knuuti J, Kalliokoski KK. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins. J Physiol 578: 347-358, 2007. (Pubitemid 44971131)
29. Holt HB, Wild SH, Wareham N, Ekelund U, Umpleby M, Shojaee-Moradie F, Holt RI, Phillips DI, Byrne CD. Differential effects of fatness, fitness and physical activity energy expenditure on whole-body, liver and fat insulin sensitivity. Diabetologia 50: 1698-1706, 2007. (Pubitemid 47036650)
30. Hsieh SD, Yoshinaga H, Muto T, Sakurai Y. Regular physical activity and coronary risk factors in Japanese men. Circulation 97: 661-665, 1998. (Pubitemid 28090959)
31. Hui JM, Kench JG, Chitturi S, Sud A, Farrell GC, Byth K, Hall P, Khan M, George J. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Hepatology 38: 420-427, 2003. (Pubitemid 36919863)
32. Iozzo P, Takala T, Oikonen V, Bergman J, Gronroos T, Ferrannini E, Nuutila P, Knuuti J. Effect of training status on regional disposal of circulating free fatty acids in the liver and skeletal muscle during physiological hyperinsulinemia. Diabetes Care 27: 2172-2177, 2004. (Pubitemid 39167181)
33. Johnson NA, George J. Fitness versus fatness: moving beyond weight loss in nonalcoholic fatty liver disease. Hepatology 52: 370-381, 2010.
34. Johnson NA, Sachinwalla T, Walton DW, Smith K, Armstrong A, Thompson MW, George J. Aerobic exercise training reduces hepatic and visceral lipids in obese individuals without weight loss. Hepatology 50: 1105-1112, 2009.
35. Kantartzis K, Thamer C, Peter A, Machann J, Schick F, Schraml C, Konigsrainer A, Konigsrainer I, Krober S, Niess A, Fritsche A, Haring HU, Stefan N. High cardiorespiratory fitness is an independent predictor of the reduction in liver fat during a lifestyle intervention in non-alcoholic fatty liver disease. Gut 58: 1281-1288, 2009.
36. Kirk E, Reeds DN, Finck BN, Mayurranjan SM, Patterson BW, Klein S. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction. Gastroenterology 136: 1552-1560, 2009.
37. Kistler KD, Brunt EM, Clark JM, Diehl AM, Sallis JF, Schwimmer JB. Physical activity recommendations, exercise intensity, and histological severity of nonalcoholic fatty liver disease. Am J Gastroenterol 106: 460-468, 2011.
38. Kistler KD, Molleston J, Unalp A, Abrams SH, Behling C, Schwimmer JB. Symptoms and quality of life in obese children and adolescents with non-alcoholic fatty liver disease. Aliment Pharmacol Ther 31: 396-406, 2010.
39. Kohrt WM, Malley MT, Coggan AR, Spina RJ, Ogawa T, Ehsani AA, Bourey RE, Martin WH 3rd, Holloszy JO. Effects of gender, age, and fitness level on response of VO2 max to training in 60-71 yr olds. J Appl Physiol 71: 2004-2011, 1991.
40. Kraegen EW, Clark PW, Jenkins AB, Daley EA, Chisholm DJ, Storlien LH. Development of muscle insulin resistance after liver insulin resistance in high-fat-fed rats. Diabetes 40: 1397-1403, 1991.
41. Krasnoff JB, Painter PL, Wallace JP, Bass NM, Merriman RB. Health-related fitness and physical activity in patients with nonalcoholic fatty liver disease. Hepatology 47: 1158-1166, 2008.
42. Kump DS, Booth FW. Alterations in insulin receptor signalling in the rat epitrochlearis muscle upon cessation of voluntary exercise. J Physiol 562: 829-838, 2005. (Pubitemid 40246796)
43. Kump DS, Booth FW. Sustained rise in triacylglycerol synthesis and increased epididymal fat mass when rats cease voluntary wheel running. J Physiol 565: 911-925, 2005. (Pubitemid 40908869)
44. Lawlor DA, Sattar N, Smith GD, Ebrahim S. The associations of physical activity and adiposity with alanine aminotransferase and gammaglutamyltransferase. Am J Epidemiol 161: 1081-1088, 2005. (Pubitemid 40734357)
45. Laye MJ, Thyfault JP, Stump CS, Booth FW. Inactivity induces increases in abdominal fat. J Appl Physiol 102: 1341-1347, 2007. (Pubitemid 46571026)
46. Lee IM, Hsieh CC, Paffenbarger RS Jr. Exercise intensity and longevity in men. The Harvard Alumni Health Study. JAMA 273: 1179-1184, 1995.
47. Li S, Brown MS, Goldstein JL. Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis. Proc Natl Acad Sci USA 107: 3441-3446, 2010.
48. Liu HY, Yehuda-Shnaidman E, Hong T, Han J, Pi J, Liu Z, Cao W. Prolonged exposure to insulin suppresses mitochondrial production in primary hepatocytes. J Biol Chem 284: 14087-14095, 2009.
49. McMillan KP, Kuk JL, Church TS, Blair SN, Ross R. Independent associations between liver fat, visceral adipose tissue, and metabolic risk factors in men. Appl Physiol Nutr Metab 32: 265-272, 2007.
50. Mokdad AH, Marks JS, Stroup DF, Gerberding JL. Actual causes of death in the United States, 2000. JAMA 291: 1238-1245, 2004. (Pubitemid 38541668)
51. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34: 267-273, 2003. (Pubitemid 36792858)
52. Moran TH, Bi S. Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: developmental aspects. Dev Psychobiol 48: 360-367, 2006. (Pubitemid 44090281)
53. Myers J, Prakash M, Froelicher V, Do D, Partington S, Atwood JE. Exercise capacity and mortality among men referred for exercise testing. N Engl J Med 346: 793-801, 2002. (Pubitemid 34987553)
54. Nader PR, Bradley RH, Houts RM, McRitchie SL, O'Brien M. Moderate-to-vigorous physical activity from ages 9 to 15 years. JAMA 300: 295-305, 2008. (Pubitemid 352008646)
55. Naples SP, Borengasser SJ, Rector RS, Uptergrove GM, Morris EM, Mikus CR, Koch LG, Britton SL, Ibdah JA, Thyfault JP. Skeletal muscle mitochondrial and metabolic responses to a high-fat diet in female rats bred for high and low aerobic capacity. Appl Physiol Nutr Metab 35: 151-162, 2010.
56. Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: The central role of nontriglyceride fatty acid metabolites. Hepatology 52: 774-788, 2010.
57. Nguyen-Duy TB, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral fat and liver fat are independent predictors of metabolic risk factors in men. Am J Physiol Endocrinol Metab 284: E1065-E1071, 2003. (Pubitemid 36617450)
58. Nobili V, Day C. Childhood NAFLD: a ticking time-bomb? Gut 58: 1442, 2009.
59. Nobili V, Manco M, Ciampalini P, Alisi A, Devito R, Bugianesi E, Marcellini M, Marchesini G. Metformin use in children with nonalcoholic fatty liver disease: an open-label, 24-month, observational pilot study. Clin Ther 30: 1168-1176, 2008. (Pubitemid 351978124)
60. Nobili V, Pinzani M. Paediatric non-alcoholic fatty liver disease. Gut 59: 561-564, 2010.
61. Noland RC, Thyfault JP, Henes ST, Whitfield BR, Woodlief TL, Evans JR, Lust JA, Britton SL, Koch LG, Dudek RW, Dohm GL, Cortright RN, Lust RM. Artificial selection for high-capacity endurance running is protective against high-fat diet-induced insulin resistance. Am J Physiol Endocrinol Metab 293: E31-E41, 2007. (Pubitemid 47105913)
62. Ogden CL, Carroll MD, Curtin LR, Lamb MM, Flegal KM. Prevalence of high body mass index in US children and adolescents, 2007-2008. JAMA 303: 242-249, 2010.
63. Oguma Y, Sesso HD, Paffenbarger RS Jr, Lee IM. Physical activity and all cause mortality in women: a review of the evidence. Br J Sports Med 36: 162-172, 2002. (Pubitemid 34651932)
64. Olsen RH, Krogh-Madsen R, Thomsen C, Booth FW, Pedersen BK. Metabolic responses to reduced daily steps in healthy nonexercising men. JAMA 299: 1261-1263, 2008. (Pubitemid 351439093)
65. Ong JP, Pitts A, Younossi ZM. Increased overall mortality and liverrelated mortality in non-alcoholic fatty liver disease. J Hepatol 49: 608-612, 2008.
66. Paffenbarger RS Jr, Hyde RT, Wing AL, Lee IM, Jung DL, Kampert JB. The association of changes in physical-activity level and other lifestyle characteristics with mortality among men. N Engl J Med 328: 538-545, 1993. (Pubitemid 23053830)
67. Perseghin G. Viewpoints on the way to a consensus session: where does insulin resistance start? The liver. Diabetes Care 32, Suppl 2: S164-S167, 2009.
68. Perseghin G, Lattuada G, De Cobelli F, Ragogna F, Ntali G, Esposito A, Belloni E, Canu T, Terruzzi I, Scifo P, Del Maschio A, Luzi L. Habitual physical activity is associated with intrahepatic fat content in humans. Diabetes Care 30: 683-688, 2007. (Pubitemid 46354353)
69. Rector RS, Thyfault JP, Laye MJ, Morris RT, Borengasser SJ, Uptergrove GM, Chakravarthy MV, Booth FW, Ibdah JA. Cessation of daily exercise dramatically alters precursors of hepatic steatosis in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. J Physiol 586: 4241-4249, 2008.
70. Rector RS, Thyfault JP, Morris RT, Laye MJ, Borengasser SJ, Booth FW, Ibdah JA. Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty rats. Am J Physiol Gastrointest Liver Physiol 294: G619-G626, 2008. (Pubitemid 351468778)
71. Rector RS, Thyfault JP, Uptergrove GM, Morris EM, Naples SP, Borengasser SJ, Mikus CR, Laye MJ, Laughlin MH, Booth FW, Ibdah JA. Mitochondrial dysfunction precedes insulin resistance and hepatic steatosis and contributes to the natural history of non-alcoholic fatty liver disease in an obese rodent model. J Hepatol 52: 727-736, 2010.
72. Rector RS, Thyfault JP, Wei Y, Ibdah JA. Non-alcoholic fatty liver disease and the metabolic syndrome: An update. World J Gastroenterol 14: 185-192, 2008. (Pubitemid 351314297)
73. Rector RS, Uptergrove GM, Morris EM, Borengasser SJ, Laughlin MH, Booth FW, Thyfault JP, Ibdah JA. Daily exercise versus caloric restriction for prevention of nonalcoholic fatty liver disease in the OLETF rat model. Am J Physiol Gastrointest Liver Physiol 300: G874-G883, 2011.
74. Reeves MJ, Rafferty AP. Healthy lifestyle characteristics among adults in the United States, 2000. Arch Intern Med 165: 854-857, 2005. (Pubitemid 40563230)
75. Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, Romanelli AJ, Shulman GI. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 279: 32345-32353, 2004. (Pubitemid 39014687)
76. Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics 118: 1388-1393, 2006. (Pubitemid 46393782)
77. Shojaee-Moradie F, Baynes KC, Pentecost C, Bell JD, Thomas EL, Jackson NC, Stolinski M, Whyte M, Lovell D, Bowes SB, Gibney J, Jones RH, Umpleby AM. Exercise training reduces fatty acid availability and improves the insulin sensitivity of glucose metabolism. Diabetologia 50: 404-413, 2007.
78. St George A, Bauman A, Johnston A, Farrell G, Chey T, George J. Independent effects of physical activity in patients with nonalcoholic fatty liver disease. Hepatology 50: 68-76, 2009.
79. Steele RM, Brage S, Corder K, Wareham NJ, Ekelund U. Physical activity, cardiorespiratory fitness, and the metabolic syndrome in youth. J Appl Physiol 105: 342-351, 2008.
80. Stephens BR, Granados K, Zderic TW, Hamilton MT, Braun B. Effects of 1 day of inactivity on insulin action in healthy men and women: interaction with energy intake. Metabolism 60: 941-949, 2011.
81. Stubbs RJ, Hughes DA, Johnstone AM, Horgan GW, King N, Blundell JE. A decrease in physical activity affects appetite, energy, and nutrient balance in lean men feeding ad libitum. Am J Clin Nutr 79: 62-69, 2004. (Pubitemid 41132063)
82. Targher G, Bertolini L, Padovani R, Rodella S, Tessari R, Zenari L, Day C, Arcaro G. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care 30: 1212-1218, 2007. (Pubitemid 46684650)
83. Targher G, Day CP, Bonora E. Risk of cardiovascular disease in patients with nonalcoholic fatty liver disease. N Engl J Med 363: 1341-1350, 2010.
84. Thyfault JP, Rector RS, Noland RC. Metabolic inflexibility in skeletal muscle: a prelude to the cardiometabolic syndrome? J Cardiometab Synd 1: 184-189, 2006.
85. Thyfault JP, Rector RS, Uptergrove GM, Borengasser SJ, Morris EM, Wei Y, Laye MJ, Burant CF, Qi NR, Ridenhour SE, Koch LG, Britton SL, Ibdah JA. Rats selectively bred for low aerobic capacity have reduced hepatic mitochondrial oxidative capacity and susceptibility to hepatic steatosis and injury. J Physiol 587: 1805-1816, 2009.
86. Tiikkainen M, Tamminen M, Hakkinen AM, Bergholm R, Vehkavaara S, Halavaara J, Teramo K, Rissanen A, Yki-Jarvinen H. Liver-fat accumulation and insulin resistance in obese women with previous gestational diabetes. Obes Res 10: 859-867, 2002. (Pubitemid 135688898)
87. Tiniakos DG, Vos MB, Brunt EM. Nonalcoholic fatty liver disease: pathology and pathogenesis. Annu Rev Pathol 5: 145-171, 2010.
88. Tobe K, Suzuki R, Aoyama M, Yamauchi T, Kamon J, Kubota N, Terauchi Y, Matsui J, Akanuma Y, Kimura S, Tanaka J, Abe M, Ohsumi J, Nagai R, Kadowaki T. Increased expression of the sterol regulatory element-binding protein-1 gene in insulin receptor substrate-2(α/β) mouse liver. J Biol Chem 276: 38337-38340, 2001.
89. van der Heijden GJ, Wang ZJ, Chu ZD, Sauer PJ, Haymond MW, Rodriguez LM, Sunehag AL. A 12-week aerobic exercise program reduces hepatic fat accumulation and insulin resistance in obese, Hispanic adolescents. Obesity (Silver Spring) 18: 384-390, 2010.
90. Wisloff U, Najjar SM, Ellingsen O, Haram PM, Swoap S, Al-Share Q, Fernstrom M, Rezaei K, Lee SJ, Koch LG, Britton SL. Cardiovascular risk factors emerge after artificial selection for low aerobic capacity. Science 307: 418-420, 2005. (Pubitemid 40139985)
91. Yasari S, Paquette A, Charbonneau A, Gauthier MS, Savard R, Lavoie JM. Effects of ingesting a high-fat diet upon exercise-training cessation on fat accretion in the liver and adipose tissue of rats. Appl Physiol Nutr Metab 31: 367-375, 2006. (Pubitemid 44621781)
92. Younossi ZM, Diehl AM, Ong JP. Nonalcoholic fatty liver disease: an agenda for clinical research. Hepatology 35: 746-752, 2002. (Pubitemid 34258367)
93. Zelber-Sagi S, Nitzan-Kaluski D, Goldsmith R, Webb M, Zvibel I, Goldiner I, Blendis L, Halpern Z, Oren R. Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study. Hepatology 48: 1791-1798, 2008.