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Cigarette smoke exposure: A novel cofactor of NAFLD progression?
Journal of Hepatology 51 (2009) 430–432 www.elsevier.com/locate/jhep
Editorial
Cigarette smoke exposure: A novel cofactor of NAFLD progression? q Ariane Mallat*, Sophie Lotersztajn AP-HP, Groupe hospitalier Henri Mondor-Albert Chenevier, Service d’He´patologie et de Gastroente´rologie, 94000 Cre´teil, France INSERM, U955, Cre´teil et Universite´ Paris XII-Val de Marne, Cre´teil, France
See Article, pages 535–547
Cigarette smoke exposure, whether passive or active, carries a high disease burden worldwide [1]. In a recent comprehensive assessment of the mortality attributable to modifiable risk factors in the US adult population, tobacco use was held responsible for 467,000 deaths (approximately one out of five) in 2005 [2]. Despite the large body of evidence documenting the pluriorgan morbidity of tobacco, reports investigating the impact of cigarette smoking on pathogenesis of liver injury have long remained scant. Initial evidence arose from two retrospective studies suggesting that cigarette smoking may increase prevalence and/or severity of alcoholic [3] and HBV-related cirrhosis [4]. Accordingly, two recent studies in patients with primary biliary cirrhosis identified tobacco use as an independent predictor of advanced fibrosis at presentation [5,6]. In contrast, in patients with chronic hepatitis C, the impact of tobacco use on fibrosis progression remains controversial [7,8] and available data would suggest that cigarette smoking may aggravate necroinflammation, thereby contributing to accelerated fibrogenesis [7–10]. Finally, in line with the carcinogenic properties of tobacco in several organs, a number of studies indicate that cigarette smoking is associated with an increased incidence of hepatocellular carcinoma in cirrhotic patients [11–14]. Non-alcoholic fatty liver disease (NAFLD), the hepatic hallmark of the metabolic syndrome, is a worrisome
Associate Editor: C.P. Day q The authors who have taken part in this study declared that they do not have anything to disclose regarding funding from industry or conflict of interest with respect to this manuscript. * Corresponding author. Tel.: +33 (0)1 49812367; fax: +33 (0)1 49812352. E-mail address: [email protected] (A. Mallat)
rising cause of chronic liver injury closely linked to a sedentary lifestyle and habits associated with it. Besides its known impact on liver-related mortality in the subgroup of patients that progress to NASH [15], NAFLD has also been identified as an independent risk factor of atherosclerosis and cardiovascular diseases [16–18]. In this issue of the Journal, Yuan et al. provide novel evidence demonstrating that tobacco smoke exposure may accelerate the development of experimental NAFLD [19]. The study extends an earlier report from the group showing that in apo B transgenic mice, chronic environmental (second-hand) smoke exposure is associated to features of atherosclerotic plaque initiation [20]. Using the same model, the authors now show that exposure to second-hand smoke potentiates steatogenesis elicited by a high-fat diet, as assessed by red oil staining and hepatic triglyceride quantification [19]. Since increased hepatic lipogenesis has been shown to account for approximately 30% of triglyceride accumulation in steatotic livers [21], the authors subsequently investigate the impact of second-hand smoke on liver lipogenic pathways. Interestingly, cultured hepatocyte cell lines exposed to second-hand smoke display enhanced accumulation of triglycerides and increased expression of Acetyl CoA Carboxylase (ACC) and Fatty acid synthase (FAS), two key enzymes governing hepatic synthesis of fatty acids. These data therefore indicate that the steatogenic properties of tobacco smoke are at least partly explained by a direct effect on hepatocytes. In deciphering molecular determinants underlying tobacco-dependent activation of lipogenesis, the authors focus on two key regulators of lipid metabolism, Sterol regulatory element binding protein-1c (SREBP-1c) and AMP-activated protein kinase (AMP kinase). SREBPs are a family of basic-helix-loop-helix-leucine zipper
0168-8278/$36.00 Ó 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jhep.2009.05.021
A. Mallat, S. Lotersztajn / Journal of Hepatology 51 (2009) 430–432
transcription factors synthesized as inactive precursors embedded in the endoplasmic reticulum [22]. Activation of SREBPs requires proteolytic cleavage, thereby allowing nuclear translocation and transcriptional activation of target lipogenic genes [23]. Whereas SREBP-2 governs synthesis of cholesterol, SREBP-1c promotes biosynthesis of fatty acids by upregulating enzymes such as ACC and FAS. The serine/threonine protein kinase AMP kinase is an energy sensor that acts as a metabolic master switch [24]. The phosphorylated active form of the enzyme simultaneously inhibits energy-consuming biosynthetic pathways such as lipogenesis and activates ATP-producing catabolic pathways such as fatty acid oxidation [24]. It has been shown that AMP kinase inhibits fatty acid synthesis both by phosphorylating target lipogenic enzymes and downregulating expression of transcription factors such as SREBP-1c [25–27]. In accordance with these data, Yuan et al. now demonstrate that second-hand smoke exposure inhibits phosphorylation and activation of AMP kinase, thereby resulting in increased SREBP-1 activity and enhancement of fatty acid synthesis [19]. This study provides compelling experimental evidence supporting a role of tobacco smoke exposure as a cofactor of NAFLD. In line with the present report, second-hand smoke exposure has also recently been shown to enhance alcoholic steatosis in a model of apoE = mice fed an alcohol diet for 4 weeks [28]; however, in animals fed a control diet, tobacco smoke exposure had no effect on liver triglyceride concentration [28]. Taken together, these data suggest that tobacco exposure may behave as a cofactor of steatogenesis of diverse origins, by enhancing hepatocyte lipogenesis. Nonetheless, the data by Yuan et al. warrant confirmation in classical models of NAFLD, such as genetically obese leptin deficient ob/ob mice or mice fed a high-fat diet; indeed, apoB transgenic mice fed a high-fat diet are primarily used as a model of atherosclerosis. Moreover, the data also raise several questions with respect to the mechanisms underlying steatogenic properties of second-hand smoke. Thus, besides the aforementioned enhancement in hepatic lipogenesis, sources of hepatic lipids in the steatotic liver include increased lipolysis in the insulin-resistant adipose tissue, reduced channeling of fatty acids to the b-oxidation pathway in the liver, and/or reduced fat export in the form of very low-density lipoproteins [23]. Future experiments should therefore investigate the impact of tobacco smoke exposure on these pathways, in particular on fatty acid influx, inasmuch as recent studies indicate that tobacco exposure predisposes to the development of insulin resistance [29,30]. Also, it is well established that AMP kinase is a major inhibitor of liver glucose output and mediates the hypoglycaemic effects of adiponectin and of anti-diabetic drugs such as metformin and thiazolinediones
431
[24,25]. These data therefore suggest that tobacco smoke might enhance insulin resistance by inhibiting hepatic AMP kinase. Interestingly, the authors previously showed that second-hand smoke exposure reduces serum levels of adiponectin in apoB mice [20]. Whether this decrease in adiponectin contributes to the tobacco-dependent inhibition of AMP kinase remains to be investigated. Finally, the data reported by Yuan et al. raise the question as to the clinical relevance of these experimental findings, an issue that remains open, given the scarcity of data. As already mentioned, it has been shown that tobacco use predisposes to the development of insulin resistance [17,31,32]. Moreover, findings from a large survey of US adolescents indicate that passive and active smoke exposure are strong independent predictors of the presence of the metabolic syndrome [33]. These observations indirectly suggest that tobacco use may indeed enhance NAFLD, the hepatic hallmark of the metabolic syndrome. However, very few studies have specifically evaluated the potential impact of tobacco use on metabolic steatosis heretofore and results have been discrepant. Thus, a cross-sectional German health survey in 2500 adults found no relationship between tobacco use and the presence of NAFLD as assessed by ultrasonography [34]. In contrast, in a longitudinal study of 368 males with a suspicion of NAFLD, as defined by unexplained ALAT elevations, onset of smoking during the course of follow-up was an independent predictor of ALAT deterioration [35]. In summary, accumulating data suggest that passive or active tobacco exposure may belong to environmental stressors contributing to the progression of liver injury. The report by Yuan et al. extends this assumption to NAFLD and provides compelling evidence indicating that tobacco smoke might alter the regulatory effect of AMP kinase on lipid metabolism. Future studies should closely investigate the clinical relevance of these findings. Nevertheless, in the meantime, tobacco cessation might be considered in the management of patients with NAFLD. References [1] Barnoya J, Glantz SA. Cardiovascular effects of secondhand smoke: nearly as large as smoking. Circulation 2005;111:2684–2698. [2] Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJ, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 2009;6:e1000058. [3] Klatsky AL, Armstrong MA. Alcohol, smoking, coffee, and cirrhosis. Am J Epidemiol 1992;136:1248–1257. [4] Yu MW, Hsu FC, Sheen IS, Chu CM, Lin DY, Chen CJ, et al. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. Am J Epidemiol 1997;145:1039–1047.
432
A. Mallat, S. Lotersztajn / Journal of Hepatology 51 (2009) 430–432
[5] Zein CO, Beatty K, Post AB, Logan L, Debanne S, McCullough AJ. Smoking and increased severity of hepatic fibrosis in primary biliary cirrhosis: a cross validated retrospective assessment. Hepatology 2006;44:1564–1571. [6] Corpechot C, Gaourar F, Chre´tien Y, Chazouille`res O, Callender ME. Is smokin a risk factor of more severe disease in rimary biliary cirrhosis? J Hepatol 2009;50 (Suppl. 1):S242–S243. [7] Pessione F, Ramond MJ, Njapoum C, Duchatelle V, Degott C, Erlinger S, et al. Cigarette smoking and hepatic lesions in patients with chronic hepatitis C. Hepatology 2001;34:121–125. [8] Hezode C, Lonjon I, Roudot-Thoraval F, Mavier JP, Pawlotsky JM, Zafrani ES, et al. Impact of smoking on histological liver lesions in chronic hepatitis C. Gut 2003;52:126–129. [9] Wang CS, Wang ST, Chang TT, Yao WJ, Chou P. Smoking and alanine aminotransferase levels in hepatitis C virus infection: implications for prevention of hepatitis C virus progression. Arch Intern Med 2002;162:811–815. [10] Mallat A, Hezode C, Lotersztajn S. Environmental factors as disease accelerators during chronic hepatitis C. J Hepatol 2008;48:657–665. [11] Jee SH, Ohrr H, Sull JW, Samet JM. Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. J Natl Cancer Inst 2004;96:1851–1856. [12] Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol 2005;42:218–224. [13] Chen ZM, Liu BQ, Boreham J, Wu YP, Chen JS, Peto R. Smoking and liver cancer in China: case-control comparison of 36,000 liver cancer deaths vs. 17,000 cirrhosis deaths. Int J Cancer 2003;107:106–112. [14] Fujita Y, Shibata A, Ogimoto I, Kurozawa Y, Nose T, Yoshimura T, et al. The effect of interaction between hepatitis C virus and cigarette smoking on the risk of hepatocellular carcinoma. Br J Cancer 2006;94:737–739. [15] Parekh S, Anania FA. Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic fatty liver disease. Gastroenterology 2007;132:2191–2207. [16] Hamaguchi M, Kojima T, Takeda N, Nagata C, Takeda J, Sarui H, et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol 2007;13:1579–1584. [17] Targher G, Alberiche M, Zenere MB, Bonadonna RC, Muggeo M, Bonora E. Cigarette smoking and insulin resistance in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1997;82:3619–3624. [18] Targher G, Bertolini L, Poli F, Rodella S, Scala L, Tessari R, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 2005;54:3541–3546. [19] Yuan H, Shyy J-YJ, Martins-Green M. Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1. J Hepatol 2009;51:535–547. [20] Yuan H, Wong LS, Bhattacharya M, Ma C, Zafarani M, Yao M, et al. The effects of second-hand smoke on biological
[21]
[22]
[23]
[24] [25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
processes important in atherogenesis. BMC Cardiovasc Disord 2007;7:1. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005;115:1343–1351. Raghow R, Yellaturu C, Deng X, Park EA, Elam MB. SREBPs: the crossroads of physiological and pathological lipid homeostasis. Trends Endocrinol Metab 2008;19:65–73. Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 2008;118:829–838. Long YC, Zierath JR. AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest 2006;116:1776–1783. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167–1174. Foretz M, Ancellin N, Andreelli F, Saintillan Y, Grondin P, Kahn A, et al. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 2005;54:1331–1339. Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, et al. Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J Physiol 2006;574:41–53. Bailey SM, Mantena SK, Millender-Swain T, Cakir Y, Jhala NC, Chhieng D, et al. Ethanol and tobacco smoke increase hepatic steatosis and hypoxia in the hypercholesterolemic apoE( / ) mouse: implications for a multihit hypothesis of fatty liver disease. Free Radic Biol Med 2009;46:928–938. Reaven GM. Insulin resistance/compensatory hyperinsulinemia, essential hypertension, and cardiovascular disease. J Clin Endocrinol Metab 2003;88:2399–2403. Henkin L, Zaccaro D, Haffner S, Karter A, Rewers M, Sholinsky P, et al. Cigarette smoking, environmental tobacco smoke exposure and insulin sensitivity: the Insulin Resistance Atherosclerosis Study. Ann Epidemiol 1999;9:290–296. Ronnemaa T, Ronnemaa EM, Puukka P, Pyorala K, Laakso M. Smoking is independently associated with high plasma insulin levels in nondiabetic men. Diabetes Care 1996;19:1229–1232. Carnethon MR, Fortmann SP, Palaniappan L, Duncan BB, Schmidt MI, Chambless LE. Risk factors for progression to incident hyperinsulinemia: the Atherosclerosis Risk in Communities Study, 1987–1998. Am J Epidemiol 2003;158:1058–1067. Weitzman M, Cook S, Auinger P, Florin TA, Daniels S, Nguyen M, et al. Tobacco smoke exposure is associated with the metabolic syndrome in adolescents. Circulation 2005;112:862–869. Haenle MM, Brockmann SO, Kron M, Bertling U, Mason RA, Steinbach G, et al. Overweight, physical activity, tobacco and alcohol consumption in a cross-sectional random sample of German adults. BMC Public Health 2006;6:233. Suzuki A, Lindor K, St. Saver J, Lymp J, Mendes F, Muto A, et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol 2005;43:1060–1066.
Editorial
Cigarette smoke exposure: A novel cofactor of NAFLD progression? q Ariane Mallat*, Sophie Lotersztajn AP-HP, Groupe hospitalier Henri Mondor-Albert Chenevier, Service d’He´patologie et de Gastroente´rologie, 94000 Cre´teil, France INSERM, U955, Cre´teil et Universite´ Paris XII-Val de Marne, Cre´teil, France
See Article, pages 535–547
Cigarette smoke exposure, whether passive or active, carries a high disease burden worldwide [1]. In a recent comprehensive assessment of the mortality attributable to modifiable risk factors in the US adult population, tobacco use was held responsible for 467,000 deaths (approximately one out of five) in 2005 [2]. Despite the large body of evidence documenting the pluriorgan morbidity of tobacco, reports investigating the impact of cigarette smoking on pathogenesis of liver injury have long remained scant. Initial evidence arose from two retrospective studies suggesting that cigarette smoking may increase prevalence and/or severity of alcoholic [3] and HBV-related cirrhosis [4]. Accordingly, two recent studies in patients with primary biliary cirrhosis identified tobacco use as an independent predictor of advanced fibrosis at presentation [5,6]. In contrast, in patients with chronic hepatitis C, the impact of tobacco use on fibrosis progression remains controversial [7,8] and available data would suggest that cigarette smoking may aggravate necroinflammation, thereby contributing to accelerated fibrogenesis [7–10]. Finally, in line with the carcinogenic properties of tobacco in several organs, a number of studies indicate that cigarette smoking is associated with an increased incidence of hepatocellular carcinoma in cirrhotic patients [11–14]. Non-alcoholic fatty liver disease (NAFLD), the hepatic hallmark of the metabolic syndrome, is a worrisome
Associate Editor: C.P. Day q The authors who have taken part in this study declared that they do not have anything to disclose regarding funding from industry or conflict of interest with respect to this manuscript. * Corresponding author. Tel.: +33 (0)1 49812367; fax: +33 (0)1 49812352. E-mail address: [email protected] (A. Mallat)
rising cause of chronic liver injury closely linked to a sedentary lifestyle and habits associated with it. Besides its known impact on liver-related mortality in the subgroup of patients that progress to NASH [15], NAFLD has also been identified as an independent risk factor of atherosclerosis and cardiovascular diseases [16–18]. In this issue of the Journal, Yuan et al. provide novel evidence demonstrating that tobacco smoke exposure may accelerate the development of experimental NAFLD [19]. The study extends an earlier report from the group showing that in apo B transgenic mice, chronic environmental (second-hand) smoke exposure is associated to features of atherosclerotic plaque initiation [20]. Using the same model, the authors now show that exposure to second-hand smoke potentiates steatogenesis elicited by a high-fat diet, as assessed by red oil staining and hepatic triglyceride quantification [19]. Since increased hepatic lipogenesis has been shown to account for approximately 30% of triglyceride accumulation in steatotic livers [21], the authors subsequently investigate the impact of second-hand smoke on liver lipogenic pathways. Interestingly, cultured hepatocyte cell lines exposed to second-hand smoke display enhanced accumulation of triglycerides and increased expression of Acetyl CoA Carboxylase (ACC) and Fatty acid synthase (FAS), two key enzymes governing hepatic synthesis of fatty acids. These data therefore indicate that the steatogenic properties of tobacco smoke are at least partly explained by a direct effect on hepatocytes. In deciphering molecular determinants underlying tobacco-dependent activation of lipogenesis, the authors focus on two key regulators of lipid metabolism, Sterol regulatory element binding protein-1c (SREBP-1c) and AMP-activated protein kinase (AMP kinase). SREBPs are a family of basic-helix-loop-helix-leucine zipper
0168-8278/$36.00 Ó 2009 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.jhep.2009.05.021
A. Mallat, S. Lotersztajn / Journal of Hepatology 51 (2009) 430–432
transcription factors synthesized as inactive precursors embedded in the endoplasmic reticulum [22]. Activation of SREBPs requires proteolytic cleavage, thereby allowing nuclear translocation and transcriptional activation of target lipogenic genes [23]. Whereas SREBP-2 governs synthesis of cholesterol, SREBP-1c promotes biosynthesis of fatty acids by upregulating enzymes such as ACC and FAS. The serine/threonine protein kinase AMP kinase is an energy sensor that acts as a metabolic master switch [24]. The phosphorylated active form of the enzyme simultaneously inhibits energy-consuming biosynthetic pathways such as lipogenesis and activates ATP-producing catabolic pathways such as fatty acid oxidation [24]. It has been shown that AMP kinase inhibits fatty acid synthesis both by phosphorylating target lipogenic enzymes and downregulating expression of transcription factors such as SREBP-1c [25–27]. In accordance with these data, Yuan et al. now demonstrate that second-hand smoke exposure inhibits phosphorylation and activation of AMP kinase, thereby resulting in increased SREBP-1 activity and enhancement of fatty acid synthesis [19]. This study provides compelling experimental evidence supporting a role of tobacco smoke exposure as a cofactor of NAFLD. In line with the present report, second-hand smoke exposure has also recently been shown to enhance alcoholic steatosis in a model of apoE = mice fed an alcohol diet for 4 weeks [28]; however, in animals fed a control diet, tobacco smoke exposure had no effect on liver triglyceride concentration [28]. Taken together, these data suggest that tobacco exposure may behave as a cofactor of steatogenesis of diverse origins, by enhancing hepatocyte lipogenesis. Nonetheless, the data by Yuan et al. warrant confirmation in classical models of NAFLD, such as genetically obese leptin deficient ob/ob mice or mice fed a high-fat diet; indeed, apoB transgenic mice fed a high-fat diet are primarily used as a model of atherosclerosis. Moreover, the data also raise several questions with respect to the mechanisms underlying steatogenic properties of second-hand smoke. Thus, besides the aforementioned enhancement in hepatic lipogenesis, sources of hepatic lipids in the steatotic liver include increased lipolysis in the insulin-resistant adipose tissue, reduced channeling of fatty acids to the b-oxidation pathway in the liver, and/or reduced fat export in the form of very low-density lipoproteins [23]. Future experiments should therefore investigate the impact of tobacco smoke exposure on these pathways, in particular on fatty acid influx, inasmuch as recent studies indicate that tobacco exposure predisposes to the development of insulin resistance [29,30]. Also, it is well established that AMP kinase is a major inhibitor of liver glucose output and mediates the hypoglycaemic effects of adiponectin and of anti-diabetic drugs such as metformin and thiazolinediones
431
[24,25]. These data therefore suggest that tobacco smoke might enhance insulin resistance by inhibiting hepatic AMP kinase. Interestingly, the authors previously showed that second-hand smoke exposure reduces serum levels of adiponectin in apoB mice [20]. Whether this decrease in adiponectin contributes to the tobacco-dependent inhibition of AMP kinase remains to be investigated. Finally, the data reported by Yuan et al. raise the question as to the clinical relevance of these experimental findings, an issue that remains open, given the scarcity of data. As already mentioned, it has been shown that tobacco use predisposes to the development of insulin resistance [17,31,32]. Moreover, findings from a large survey of US adolescents indicate that passive and active smoke exposure are strong independent predictors of the presence of the metabolic syndrome [33]. These observations indirectly suggest that tobacco use may indeed enhance NAFLD, the hepatic hallmark of the metabolic syndrome. However, very few studies have specifically evaluated the potential impact of tobacco use on metabolic steatosis heretofore and results have been discrepant. Thus, a cross-sectional German health survey in 2500 adults found no relationship between tobacco use and the presence of NAFLD as assessed by ultrasonography [34]. In contrast, in a longitudinal study of 368 males with a suspicion of NAFLD, as defined by unexplained ALAT elevations, onset of smoking during the course of follow-up was an independent predictor of ALAT deterioration [35]. In summary, accumulating data suggest that passive or active tobacco exposure may belong to environmental stressors contributing to the progression of liver injury. The report by Yuan et al. extends this assumption to NAFLD and provides compelling evidence indicating that tobacco smoke might alter the regulatory effect of AMP kinase on lipid metabolism. Future studies should closely investigate the clinical relevance of these findings. Nevertheless, in the meantime, tobacco cessation might be considered in the management of patients with NAFLD. References [1] Barnoya J, Glantz SA. Cardiovascular effects of secondhand smoke: nearly as large as smoking. Circulation 2005;111:2684–2698. [2] Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJ, et al. The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle, and metabolic risk factors. PLoS Med 2009;6:e1000058. [3] Klatsky AL, Armstrong MA. Alcohol, smoking, coffee, and cirrhosis. Am J Epidemiol 1992;136:1248–1257. [4] Yu MW, Hsu FC, Sheen IS, Chu CM, Lin DY, Chen CJ, et al. Prospective study of hepatocellular carcinoma and liver cirrhosis in asymptomatic chronic hepatitis B virus carriers. Am J Epidemiol 1997;145:1039–1047.
432
A. Mallat, S. Lotersztajn / Journal of Hepatology 51 (2009) 430–432
[5] Zein CO, Beatty K, Post AB, Logan L, Debanne S, McCullough AJ. Smoking and increased severity of hepatic fibrosis in primary biliary cirrhosis: a cross validated retrospective assessment. Hepatology 2006;44:1564–1571. [6] Corpechot C, Gaourar F, Chre´tien Y, Chazouille`res O, Callender ME. Is smokin a risk factor of more severe disease in rimary biliary cirrhosis? J Hepatol 2009;50 (Suppl. 1):S242–S243. [7] Pessione F, Ramond MJ, Njapoum C, Duchatelle V, Degott C, Erlinger S, et al. Cigarette smoking and hepatic lesions in patients with chronic hepatitis C. Hepatology 2001;34:121–125. [8] Hezode C, Lonjon I, Roudot-Thoraval F, Mavier JP, Pawlotsky JM, Zafrani ES, et al. Impact of smoking on histological liver lesions in chronic hepatitis C. Gut 2003;52:126–129. [9] Wang CS, Wang ST, Chang TT, Yao WJ, Chou P. Smoking and alanine aminotransferase levels in hepatitis C virus infection: implications for prevention of hepatitis C virus progression. Arch Intern Med 2002;162:811–815. [10] Mallat A, Hezode C, Lotersztajn S. Environmental factors as disease accelerators during chronic hepatitis C. J Hepatol 2008;48:657–665. [11] Jee SH, Ohrr H, Sull JW, Samet JM. Cigarette smoking, alcohol drinking, hepatitis B, and risk for hepatocellular carcinoma in Korea. J Natl Cancer Inst 2004;96:1851–1856. [12] Marrero JA, Fontana RJ, Fu S, Conjeevaram HS, Su GL, Lok AS. Alcohol, tobacco and obesity are synergistic risk factors for hepatocellular carcinoma. J Hepatol 2005;42:218–224. [13] Chen ZM, Liu BQ, Boreham J, Wu YP, Chen JS, Peto R. Smoking and liver cancer in China: case-control comparison of 36,000 liver cancer deaths vs. 17,000 cirrhosis deaths. Int J Cancer 2003;107:106–112. [14] Fujita Y, Shibata A, Ogimoto I, Kurozawa Y, Nose T, Yoshimura T, et al. The effect of interaction between hepatitis C virus and cigarette smoking on the risk of hepatocellular carcinoma. Br J Cancer 2006;94:737–739. [15] Parekh S, Anania FA. Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic fatty liver disease. Gastroenterology 2007;132:2191–2207. [16] Hamaguchi M, Kojima T, Takeda N, Nagata C, Takeda J, Sarui H, et al. Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease. World J Gastroenterol 2007;13:1579–1584. [17] Targher G, Alberiche M, Zenere MB, Bonadonna RC, Muggeo M, Bonora E. Cigarette smoking and insulin resistance in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1997;82:3619–3624. [18] Targher G, Bertolini L, Poli F, Rodella S, Scala L, Tessari R, et al. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes 2005;54:3541–3546. [19] Yuan H, Shyy J-YJ, Martins-Green M. Second-hand smoke stimulates lipid accumulation in the liver by modulating AMPK and SREBP-1. J Hepatol 2009;51:535–547. [20] Yuan H, Wong LS, Bhattacharya M, Ma C, Zafarani M, Yao M, et al. The effects of second-hand smoke on biological
[21]
[22]
[23]
[24] [25]
[26]
[27]
[28]
[29]
[30]
[31]
[32]
[33]
[34]
[35]
processes important in atherogenesis. BMC Cardiovasc Disord 2007;7:1. Donnelly KL, Smith CI, Schwarzenberg SJ, Jessurun J, Boldt MD, Parks EJ. Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease. J Clin Invest 2005;115:1343–1351. Raghow R, Yellaturu C, Deng X, Park EA, Elam MB. SREBPs: the crossroads of physiological and pathological lipid homeostasis. Trends Endocrinol Metab 2008;19:65–73. Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 2008;118:829–838. Long YC, Zierath JR. AMP-activated protein kinase signaling in metabolic regulation. J Clin Invest 2006;116:1776–1783. Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167–1174. Foretz M, Ancellin N, Andreelli F, Saintillan Y, Grondin P, Kahn A, et al. Short-term overexpression of a constitutively active form of AMP-activated protein kinase in the liver leads to mild hypoglycemia and fatty liver. Diabetes 2005;54:1331–1339. Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, et al. Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hepatic disorders. J Physiol 2006;574:41–53. Bailey SM, Mantena SK, Millender-Swain T, Cakir Y, Jhala NC, Chhieng D, et al. Ethanol and tobacco smoke increase hepatic steatosis and hypoxia in the hypercholesterolemic apoE( / ) mouse: implications for a multihit hypothesis of fatty liver disease. Free Radic Biol Med 2009;46:928–938. Reaven GM. Insulin resistance/compensatory hyperinsulinemia, essential hypertension, and cardiovascular disease. J Clin Endocrinol Metab 2003;88:2399–2403. Henkin L, Zaccaro D, Haffner S, Karter A, Rewers M, Sholinsky P, et al. Cigarette smoking, environmental tobacco smoke exposure and insulin sensitivity: the Insulin Resistance Atherosclerosis Study. Ann Epidemiol 1999;9:290–296. Ronnemaa T, Ronnemaa EM, Puukka P, Pyorala K, Laakso M. Smoking is independently associated with high plasma insulin levels in nondiabetic men. Diabetes Care 1996;19:1229–1232. Carnethon MR, Fortmann SP, Palaniappan L, Duncan BB, Schmidt MI, Chambless LE. Risk factors for progression to incident hyperinsulinemia: the Atherosclerosis Risk in Communities Study, 1987–1998. Am J Epidemiol 2003;158:1058–1067. Weitzman M, Cook S, Auinger P, Florin TA, Daniels S, Nguyen M, et al. Tobacco smoke exposure is associated with the metabolic syndrome in adolescents. Circulation 2005;112:862–869. Haenle MM, Brockmann SO, Kron M, Bertling U, Mason RA, Steinbach G, et al. Overweight, physical activity, tobacco and alcohol consumption in a cross-sectional random sample of German adults. BMC Public Health 2006;6:233. Suzuki A, Lindor K, St. Saver J, Lymp J, Mendes F, Muto A, et al. Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease. J Hepatol 2005;43:1060–1066.