2009, Number S1
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Ann Hepatol 2009; 8 (S1)
Is exercise an effective treatment for NASH? Knowns and unknowns
Caldwell S, Lazo M
Language: English
References: 48
Page: 60-66
PDF size: 87.47 Kb.
Text Extraction
Non-alcoholic steatohepatitis has emerged as one of the most common causes of chronic liver disease in many regions of the world. Exercise and dietary changes constitute cornerstones of overall therapy aimed at achieving weight loss in hopes of ameliorating lipid-induced hepatocellular injury by mobilizing fat out of the liver. Indeed weight loss is known to be effective as evident in several controlled trials and, in the extreme, with bariatric surgery. However, less is known about exercise in the absence of weight loss especially in terms of altering hepatic fat metabolism. As with steatosis, adipose tissue function and other targets of insulin activity, skeletal muscle physiology is closely integrated with overall energy homeostasis and calorie disposal. Although much remains to be learned, increased physical conditioning appears to be closely linked to improved hepatic metabolism independent of changes in body weight. This is of practical importance to patients attempting lifestyle changes who may become unnecessarily discouraged if there is not evidence of associated weight loss as a result of increased activity. Moreover, the degree of physical conditioning represents an unmeasured and potentially confounding variable in most clinical trials of pharmacological intervention in NASH. Clinical investigation is needed to better understand the effects of exercise on liver fat metabolism and on how best to measure the degree of physical conditioning both as a baseline indicator of overall energy homeostasis and an end-point of treatment.
REFERENCES
Fournier E, Peresson R, Guy G, Hermier D. Relationship between storage and secretion of hepatic lipids in two breeds of geese with different susceptibility to liver steatosis. Poultry Science 1997; 76: 599-607.
Hermier D, Guy G, Guillaumin S, Davail S, Andre JM, Hoo-Paris R. Differential channelling of liver lipids in relation to susceptibility to hepatic steatosis in two species of ducks. Comparative Biochemistry & Physiology. Part B, Biochemistry & Molecular Biology 2003; 135: 663-75.
Molee W, Bouillier-Oudot M, Auvergne A, Babile R. Changes in lipid composition of hepatocyte plasma membrane induced by overfeeding in duck. Comparative Biochemistry & Physiology Part B, Biochemistry & Molecular Biology 2005; 141: 437-44.
Zomborszky Z, Husveth F. Liver total lipids and fatty acid composition of shot red and fallow deer males in various reproduction periods. Comparative Biochemistry and Physiology Part A 2000; 126: 107-114.
Hermier D, Saadoun A, Salichon M-R, Sellier N, Rousselot-Paillet D, Chapman MJ. Plasma lipoproteins and liver lipids in two breeds of geese with different susceptibility to hepatic steatosis: Changes induced by development and forced-feeding. Lipids 1991; 26: 331-339.
Pelsers MM, Butler PJ, Bishop CM, Glatz JFC. Fatty acid binding protein in hear and skeletal muscles of the migratory barnacle goose throughout development. Am J Physiology 1999; 276: R637-43.
Caldwell SH, Ikura Y, Iezzoni JC, Liu Z. Has Natural Selection in Human Populations Produced Two Types of Metabolic Syndrome (with and without fatty liver)? J Gastroenterology and Hepatology 2007; 22 (Suppl 1): S11-S19.
Puri P, Baillie RA, Wiest MM, Mirshahi F, Choudhury J, Cheung O, Sargeant C, Contos MJ, Sanyal AJ. A lipidomic analysis of nonalcoholic fatty liver disease. Hepatology 2007; 46: 1081-90.
Wilfred de Alwis NM, Day CP. Genes and nonalcoholic fatty liver disease. Current Diabetes Reports 2008; 8: 156-63.
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 2008.
Stefan N, Kantartzis K, Machann J, Schick F, Thamer C, Rittig K, Balletshofer B, et al. Identification and characterization of metabolically benign obesity in humans. Arch Intern Med 2008; 168: 1609-15.
Wildman RP, Munter P, Reynolds K, McGinn AP, Rajpathak S, Wylie-Rosett J, Sowers MFR. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering. Arch Intern Med 2008; 168: 1617-1624.
Yamauchi T, Abe T, Midorikawa T, Kondo M. Body composition and resting metabolic rate of Japanese college Sumo wrestlers and non-athlete students: are Sumo wrestlers obese? Anthropological Science 2004; 112: 179-85.
Nishizawa T, Akaoka I, Nishida Y, Kawaguchi Y, Hayashi E, Yoshimura T. Some factors related to obesity in the Japanese Sumo wrestler. Am J Clin Nutrition 1976; 29: 1167-74.
Perseghin G, Lattuada G, de Cobella F, Ragogna F, Ntali G, Esposito A, et al. Habitual physical activity is associated with intrahepatic fat content in humans. Diabetes Care 2007; 30: 683-8.
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 2007; 32: 265-72.
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 2006; 130: 2023–2030.
Krasnoff JB, Painter PL, Wallace JP, Bass NM, Merriman RB. Health-related fitness and physical activity in patients with nonalcoholic fatty liver disease. Hepatology 2008; 47: 1158-1165.
Devries MC, Samjoo IA, Hamadeh MJ, Tarnopolsky MA. Effect of endurance exercise on hepatic lipid content, enzymes, and adiposity in men and women. Obesity 2008; 366: 1-8.
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 2007; 50: 404-13.
Dekker MJ, Lee S, Hudson R, Kilpatrick K, Graham TE, Ross R, Robinson LE. An exercise intervention without weight loss decreases circulating interleukin-6 in lean and obese men with and without type 2 diabetes mellitus. Metabolism 2007; 56: 332-8.
Wieckowska A, Papouchado BG, Li Z-Z, López R, Zein NN, Feldstein AE. Increased hepatic and circulating interleukin-6 levels in human nonalcoholic steatohepatitis. Am J Gastro 2007; 103: 1372-9.
Pedersen BK, Akerström TC, Nielsen AR, Fischer CP. Role of myokines in exercise and metabolism. J Appl Physiol 2007; 103: 1093-1098.
Febbraio MA, Hiscock N, Sacchetti M, Fischer CP, Pedersen BK. Interleukin-6 is a novel factor mediating glucose homeostasis during skeletal muscle contraction. Diabetes 2004; 53: 1643-8.
Bonekamp S, Barone B, Clark JM, Stewarts K J. The effect of an exercise training intervention on hepatic steatosis. Hepatology 2008; 48 (S1): 806A.
Nguyen-Duy T-B, Nichaman MZ, Church TS, Blair SN, Ross R. Visceral and liver fat are independent predictors of metabolic risk factors in men. Am J Physiol Endocrinol Metab 2003; 284: E1065-E1071.
Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R, Janssen I. Reduction in obesity and related comorbid conditions after diet-induced or exercise-induced weight loss in men. A randomized controlled trial. Ann Intern Med 2000; 133: 92-103.
Irving BA, Davis CK, Brock DW, Weltman JY, Swift D, Barrett EJ, Gaesser GA, Weltman A. Effect of exercise training on abdominal visceral fat and body composition. Medicine and Science in Sports and Exercise 2008: 1863-1872.
Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, Bales CW, Henes S, Samsa GP, Otvos JD, Kulkarni KR, Slentz CA. Effects of the amount and intensity of exercise on plasma lipoproteins. New England Journal of Medicine 2002; 347: 1483-92.
Lavoie J-M, Gauthier M-S. Regulation of fat metabolism in the liver: link to nonalcoholic hepatic steatosis and impact of physical exercise. Cell Mol Life Sci 2006; 63: 1393-1409.
Perseghin G, Scifo P, de Cobelli F, Pagliato E, Battezzati A, Arcelloni A, Vanzulli A, et al. Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans. Diabetes 1999; 48: 1600-6.
Proctor DN, Sinning WE, Walro JM, Sieck GC, Lemon PWR. Oxidative capacity of human muscle fiber types: effects of age and training status. J Appl Physiol 1995; 78: 2033-8.
Pruchnic R, Katsiaras A, He J, Kelley DE, Winters C, Goodpaster BH. Exercise training increases intramyocellular lipid and oxidative capacity in older adults. Am J Physiol Endocrinol Metab 2004; 287: E857-62.
Schrauwen-Hinderling VB, Roden M, Kooi ME, Hesselink MKC, Schrauwen P. Muscular mitochondrial dysfunction and type 2 diabetes mellitus. Current Opinion in Clinical Nutrition and Metabolic Care 2007; 10: 698-703.
Blaak EE, Wagenmakers AJM, Glatz JFC, Wolffenbuttel BHR, Kemerink GJ, Langenberg CJM, Heidendal GAK, Saris WHM. Plasma FFA utilization and fatty acid binding protein content are diminished in type 2 diabetic muscle. Am J Physiol Endocrinol Metab 2000; 279: E146-54.
Lin J, Wu H, Tarr PT, Zhang CY, Wu Z, Boss O, Michael LF, et al. Transcriptional co-activator PGC-1 alpha drives the formation of slow twitch muscle fibers. Nature 2002; 418: 797-801.
Koves TR, Li P, An J, Akimoto T, Slentz D, Ilkayeva O, Dohm GL, Yan Z, Newgard CB, Muoio DM. Peroxisome proliferator-activated receptor-gamma co-activator 1alpha-mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid-induced mitochondrial inefficiency. J Biol Chem 2005; 280: 33588-98.
Febbraio MA, Lancaster GI. Skeletal muscle: not simply an organ for locomotion and energy storage. J Physiol 2008.
Harrison SA, Day CP. Benefits of Lifestyle Modification in NAFLD. Gut 2007; 56: 1760-9.
Suzuki A, Lindor K, St Saver J, Lymp J, Mendes F, Muto A, Okada T, Angulo P. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol 2005; 43: 1060-66.
Lazo M, Solga SF, Horska A, Bonekamp S, Diehl AM, Brancati FL, Clark JM and Look Ahead Research Group. The effect of one year of intensive lifestyle intervention on hepatic steatosis. Hepatology 2008; 48(Suppl): 813A.
Ueno T, Sugawara H, Sujaku K, Hashimoto O, Tsuji R, Tamaki S, Torimura T, Inuzuka S, Sata M, Tanikawa K. Therapeutic effects of restricted diet and exercise in obese patients with fatty liver. J Hepatol 1997; 27: 103-7.
Nobili V, Manco M, Devito R, Di Ciommo V, Comparcola D, Sartorelli MR, Piemonte F, Marcellini M, Angulo P. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. Hepatology 2008; 48: 119-28.
Cotrim HP, Freitas LA, Alves E, Almeida A, May DS, Caldwell SH. Effects of light to moderate alcohol consumption on steatosis and steatohepatitis in severely obese patients. Eur J gastro and Hepatol (accepted).
Krahenbuhl S. Alcohol-induced myopathy: What is the role of mitochondria? Hepatol 2001; 34: 210-11.
Jacobsen EB, Hamberg O, Quistorff B, Ott P. Reduced mitochondrial adenosine triphosphate synthase in skeletal muscle in patients with Child-Pugh Class B and C cirrhosis. Hepatol 2001; 34: 7-12.
Lawlor DA, Sattar N, Smith GD, Ebrahim S. The associations of physical activity and adiposity with alanine aminotransferase and gamma-glutamyltransferase. Am J Epidemiology 2005; 161: 1081-8.
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 2008; 48: 1791-8.