2009, Number S1
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Ann Hepatol 2009; 8 (S1)
Metabolic syndrome and non-alcoholic fatty liver disease
Almeda-Valdés P, Cuevas-Ramos D, Aguilar-Salinas CA
Language: English
References: 47
Page: 18-24
PDF size: 81.03 Kb.
Text Extraction
The development of nonalcoholic fatty liver disease (NAFLD) is strongly associated with the metabolic syndrome as reflected by the fact that approximately 90% of the patients with NAFLD have more than one feature of metabolic syndrome and about 33% have three or more criteria. The physiopathology, epidemiology and therapeutic considerations of the disease are reviewed here. Lipotoxicity plays a predominant role in the pathophysiology of both entities. It leads to accumulation of triglycerides in the liver as a result of an imbalance among the uptake, synthesis, export, and oxidation of fatty acids. Both conditions are very common in Mexico. Using the Adult Treatment Panel diagnostic criteria, the 1994 prevalence of the metabolic syndrome was 26.6%.Although the prevalence of NAFLD is not known, but it can be estimated from the prevalence of obesity (30%). Since NAFLD is found in over two thirds of the obese subjects, this condition may exist in 20% of the adult population. The treatment of both conditions should be based in an integral approach, including the adoption of a healthy lifestyle, weight loss and may be pharmacotherapy. In summary, NAFLD is the hepatic expression of the metabolic syndrome. The study and treatment of these disorders could not be viewed as separate issues.
REFERENCES
Reaven G. Metabolic Syndrome: Pathophysiology and implications for management of cardiovascular disease. Circulation 2002; 106:86-288.
Grundy S, Brewer B, Cleeman J, Smith S, Lenfant C. Definition of metabolic syndrome: Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition. Circulation 2004; 109: 433-438.
Ruderman N, Cacicedo J, Itani S, Yagihashi N, Saha A, Ye J, Chen K, Zou M, Carling D, Boden G, Cohen R, Keaney J, Kraegen E, Ido Y. Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes. Biochem Soc Trans 2003; 31: 202-206.
Aguilar-Salinas C, Rojas R, Gómez-Pérez F, Valles V, Ríos-Torres J, Franco A, Olaiz G, Rull J, Sepúlveda J. High prevalence of metabolic syndrome in Mexico. Arch Med Res 2004; 35:76-81.
Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-1231.
Pagano C, Soardo G, Esposito W, Fallo F, Basan L, Donnini D, Federspil G, Sechi L, Vettor R. Plasma adiponectin is decreased in nonalcoholic fatty liver disease. Eur J Endocrinol 2005; 153: 113-118.
Jiang J, Torok N. Nonalcoholic steatohepatitis and the metabolic syndrome. Metab Syndr Relat Disord 2008; 6: 1-8.
Li Z, Yang S, Lin H, Huang J, Watkins P, Moser A, DeSimone C, Song X, Diehl A. Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease. Hepatology 2003; 37: 343-359.
Matteoni C, Younossi Z, Gramlich T, Boparai N, Liu Y, McCullough A. Nonalcoholic fatty liver disease: A spectrum of clinical and pathological severity. Gastroenterology 1999; 116: 1413-1419.
Olaiz-Fernández G, Rivera-Dommarco J, Shamah-Levy T, Rojas R, Villalpando-Hernández S, Hernández-Avila M, Sepúlveda-Amor J. Encuesta Nacional de Salud y Nutrición 2006. Cuernavaca, México: Instituto Nacional de Salud Pública. 2006.
Bugianesi E, McCullough A, Marchesini G. Insulin resistance: A metabolic pathway to chronic liver disease. Hepatology 2005; 42: 987-1000.
Boden G, Jadali F, White J, Liang Y, Mozzoli M, Chen X, Coleman E, Smith C. Effects of fat on insulin-stimulated carbohydrate metabolism in normal men. J Clin Invest 1991; 88: 960-966.
Roden M, Price T, Perseghuin G, Petersen K, Rothman D, Cline G, Shulman G. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 1996; 97: 2859-2865.
Ruderman N, Saha A, Vavvas D, Witters L. Malonyl-CoA, fuel sensing, and insulin resistance. Am J Physiol Endocrinol Metab 1999; 276: 1-18.
McGarry J. Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 2002; 51: 7-18.
Ruderman N, Prentki M. AMP kinase and malonyl-CoA: Targets for therapy of the metabolic syndrome. Nat Rev Drug Discov 2004; 3: 340-351.
Park H, Kaushik V, Constant S, Prentki M, Przybytkowski E, Ruderman N, Saha A. Coordinate regulation of malonyl-CoA decarboxylase, sn-glycerol-3-phosphate acyltransferase, and acetyl-CoA carboxylase by AMP-activated protein kinase in rat tissues in response to exercise. J Biol Chem 2002; 277: 32571-32577.
Boden G, Shulman G. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and b-cell dysfunction. Eur J Clin Invest 2002; 32: 14-23.
Unger R. Minireview: Weapons of lean body mass destruction: The role of ectopic lipids in the metabolic syndrome. Endocrinology 2003; 144: 5159-5165.
Grundy S, Hansen B, Smith S, Cleeman J, Kahn R. Clinical management of metabolic syndrome: Report of the American Heart Association/National Heart, Lung, and Blood Institute/American Diabetes Association Conference on Scientific Issues Related to Management. Circulation 2004; 109: 551-556.
Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M, Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S, Nagai R, Kahn B, Kadowaki T. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat. Med 2002; 8: 1288-1295.
Tomas E, Tsao T, Saha A, Murrey H, Zhang C, Itani S, Lodish H, Ruderman N. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: Acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA 2002; 99: 16309-16313.
Xu A, Wang Y, Keshaw H, Xu L, Lam K, Cooper G. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003; 112: 91-100.
Meigs J, Hu F, Rifai N, Manson J. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA 2004; 291: 1978-1986.
Hennig B, Meerarani P, Ramadass P, Watkins B, Toborek M. Fatty acid-mediated activation of vascular endothelial cells. Metabolism 2000; 49: 1006-1013.
Seppälä-Lindroos A, Vehkavaara S, Häkkinen A, Goto T, Westerbacka J, Sovijärvi A, Halavaara J, Yki-Järvinen H. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 2002; 87: 3023-3028.
Varman S, Liu Z, Qu X, Elder B, Bilz S, Befroy D, Romanelli A, Shulman G. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 2004; 279: 32345-32353.
El-Assaad W, Buteau J, Peyot M, Nolan C, Roduit R, Hardy S, Joly E, Dbaibo G, Rosenberg L, Prentki M. Saturated fatty acids synergize with elevated glucose to cause pancreatic b-cell death. Endocrinology 2003; 144: 4154-4163.
Rector RS, Thyfault JP, Wei Y, Ibdah JA. Non-alcoholic fatty liver disease and the metabolic syndrome: An update. World J Gastroenterol 2008; 14: 185-192.
Choi S, Diehl A. Hepatic triglyceride synthesis and nonalcoholic fatty liver disease. Curr Opin Lipidol 2008; 19: 295-300.
Combs T, Berg A, Obici S, Scherer P, Rossetti L. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest 2001; 108: 1875-188.
Rajala M, Scherer P. Minireview: The adipocyte-At the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 2003; 144: 3765-3773.
Hotamisligil G, Peraldi P, Budavari A, Ellis R, White M, Spiegelman B. IRS-1-Mediated inhibition of insulin receptor tyrosine-kinase activity in TNF-a-and obesity-induced insulin resistance. Science 1996; 271: 665-668.
Unger R. Lipotoxic diseases. Annu Rev Med 2002; 53: 319-336.
Leclercq IA, Farrell GC, Schriemer R, Robertson GR. Leptin is essential for the hepatic fibrogenic response to chronic liver injury. J Hepatol 2002; 27: 206-213.
Marchesini G, Bugianesi E, Forlani G, Cerrelli F, Lenzi M, Manini R, Natale S, Vanni E, Villanova N, Melchionda N, Rizzetto M. Nonalcoholic fatty liver, steatohepatitis, and the metabolic syndrome. Hepatology 2003; 37: 917-923.
Marceau P, Biron S, Hould F, Marceau S, Simard S, Thung S, Kral J. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab 1999; 84: 1513-1517.
Chitturi S, Abeygunasekera S, Farrell G, Holmes-Walker J, Hui J, Fung C, Karim R, Lin R, Samarasinghe D, Liddle C, Weltman M, George J. NASH and insulin resistance: Insulin hypersecretion and specific association with the insulin resistance syndrome. Hepatology 2002; 35: 373-379.
Ueno T, Sgawar H, Sujaku K, Hashimoto O, 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; 247: 103-107.
Luyckx F, Desaive C, Thiry A, Dewé W, Scheen A, Gielen JE, Lefèbvre P. Liver abnormalities in severely obese subjects: Effect of drastic weight loss after gastroplasty. Int J Obes 1998; 22: 222-226.
Stratopoulos C, Papakonstantinou A, Terzis I, Spiliadi C, Dimitriades G, Komesidou V, Kitsanta P, Agyrakos T, Hadjiyannakis E. Changes in liver histology accompanying massive weight loss after gastroplasty for morbid obesity. Obes Surg 2005; 15: 1154-1160.
Adams L, Angulo P. Treatment of non-alcoholic fatty liver disease. Postgrad Med J 2006; 82: 315-322.
Grundy S, Cleeman J, Merz N, Brewer B, Clark L, Hunninghake D, Pasternak R, Smith S, Stone N. Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation 2004; 110: 227-239.
Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N. Metformin in non-alcoholic steatohepatitis. Lancet 2001; 358: 893-394.
Belfort R, Harrison S, Brown K, Darland C, Finch J, Hardies J, Balas Bogdan, Gastaldelli A, Tio F, PUlcini J, Berria R, Ma J, Dwivedi S, Havranek R, Fincke C, DeFronzo R, Bannayan G, Schenker S, Cusi K. A Placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 2297-2307.
Fan C, Pan J, Usuda N, Yeldandi A, Rao S, Reddy J. Steatohepatitis, spontaneous peroxisome proliferation and liver tumors in mice lacking peroxisomal fatty acyl-CoA oxidase. J Biol Chem 1998; 273: 15639-15645.
Reaven G. Insulin resistance/compensatory hyperinsulinemia, essential hypertension, and cardiovascular disease. J Clin Endocrinol Metab 2003; 88: 2399-2403.