"Hypothesis of seven balances": Molecular mechanisms behind alcoholic liver diseases and association with PPARα

Journal of Occupational Health

Volumn 51, Issue 5, 2009, Pages 391-403

  Moriya, Takashi ^a   Naito, Hisao ^a   Ito, Yuki ^a   Nakajima, Tamie ^a  

^a NAGOYA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

Adiponectin; Alcoholic liver diseases; Fibrosis; NF B; PPAR ; TNF

Indexed keywords

IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA;

ALCOHOL LIVER DISEASE; HUMAN; INFLAMMATION; METABOLISM; MOLECULAR EPIDEMIOLOGY; OXIDATIVE STRESS; PATHOPHYSIOLOGY; PHYSIOLOGY; REVIEW;

HUMANS; INFLAMMATION; LIVER DISEASES, ALCOHOLIC; MOLECULAR EPIDEMIOLOGY; NF-KAPPA B; OXIDATIVE STRESS; PPAR ALPHA;

EID: 74549189355     PISSN: 13419145     EISSN: 13489585     Source Type: Journal    
DOI: 10.1539/joh.K9001     Document Type: Review

References (124)

1. Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. N Engl J Med 2000; 343: 1467-76.
2. Hines IN, Wheeler MD. Recent advances in alcoholic liver disease III. Role of the innate immune response in alcoholic hepatitis. Am J Physiol Gastrointest Liver Physiol 2004; 287: G310-4.
3. McClain CJ, Song Z, Barve SS, Hill DB, Deaciuc I. Recent advances in alcoholic liver disease. IV. Dysregulated cytokine metabolism in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 2004; 287: G497-502.
4. Baker A. Alcohol-related deaths by occupation: What do data for England and Wales in 2001-2005 tell us about doctors' mortality? Alcohol Alcohol 2008; 43: 121-2.
5. Cunradi CB, Greiner BA, Ragland DR, Fisher JM. Burnout and alcohol problems among urban transit operators in San Francisco. Addict Behav 2003; 28: 91-109.
6. Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem 2000; 275: 2247-50.
7. Lieber CS. Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol 2004; 34: 9-19.
8. Lieber CS. In: Medical and nutritional complications of alcoholism: Mechanisms and management. New York: Plenum Press; 1992.
9. Lieber CS, Jones DP, Decarli LM. Effects of prolonged ethanol intake: Production of fatty liver despite adequate diets. J Clin Invest 1965; 44: 1009-21.
10. Lieber CS, Lefevre A, Spritz N, Feinman L, DeCarli LM. Difference in hepatic metabolism of long- and medium-chain fatty acids: The role of fatty acid chain length in the production of the alcoholic fatty liver. J Clin Invest 1967; 46: 1451-60.
11. Lieber CS, DeCarli LM. Quantitative relationship between amount of dietary fat and severity of alcoholic fatty liver. Am J Clin Nutr 1970; 23: 474-8.
12. Wu D, Zhai Q, Shi X. Alcohol-induced oxidative stress and cell responses. J Gastroenterol Hepatol 2006; 21: S26-9.
13. Lieber CS, DeCarli LM. An experimental model of alcohol feeding and liver injury in the baboon. J Med Primatol 1974; 3: 153-63.
14. Cederbaum AI. Cytochrome P450 2E1-dependent oxidant stress and upregulation of anti-oxidant defense in liver cells. J Gastroenterol Hepatol 2006; 21: S22-5.
15. Tsutsumi M, Lasker JM, Shimizu M, Rosman AS, Lieber CS. The intralobular distribution of ethanol-inducible P450 IIE1 in rat and human liver. Hepatology 1989; 10: 437-46.
16. Takahashi T, Lasker JM, Rosman AS, Lieber CS. Induction of cytochrome P-450 2E1 in the human liver by ethanol is caused by a corresponding increase in encoding messenger RNA. Hepatology 1993; 17: 236-45.
17. Salmela KS, Kessova IG, Tsyrlov IB, Lieber CS. Respective roles of human cytochrome P-4502E1, 1A2, 3A4 in the hepatic microsomal ethanol oxidizing system. Alcohol Clin Exp Res 1998; 22: 2125-32.
18. Roach MK, Reese WN Jr, Creaven PJ. Ethanol oxidation in the microsomal fraction of rat liver. Biochem Biophys Res Commun 1969; 36: 596-602.
19. Tephly TR, Tinelli F, Watkins WD. Alcohol metabolism: role of microsomal oxidation in vivo. Science 1969; 166: 627-8.
20. Wan YJY, Morimoto M, Thurman RG, Bojes HK, French SW. Expression of the peroxisome proliferator-activated receptor gene is decreased in experimental alcoholic liver disease. Life Sciences 1995; 56: 307-17.
21. Galli A, Pinaire J, Fischer M, Dorris R, Crabb DW. The transcriptional and DNA binding activity of peroxisome proliferator-activated receptor α is inhibited by ethanol metabolism. A novel mechanism for the development of ethanol-induced fatty liver. J Biol Chem 2001; 276: 68-75.
22. Nakajima T, Kamijo Y, Tanaka N, et al. Peroxisome proliferator-activated receptor α protects against alcohol-induced liver damage. Hepatology 2004; 40: 972-80.
23. Yin M, Gabele E, Wheeler MD, et al. Alcohol-induced free radicals in mice: Direct toxicants or signaling molecules? Hepatology 2001; 34: 935-942.
24. Toyama T, Nakamura H, Harano Y, et al. PPARα ligands activate antioxidant enzymes and suppress hepatic fibrosis in rats. Biochem Biophys Res Commun 2004; 324: 697-704.
25. 2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells. Metabolism 2001; 50: 3-11.
26. Hanck C, Rossol S, Bocker U, Tokus M, Singer MV. Presence of plasma endotoxin is correlated with tumour necrosis factor receptor levels and disease activity in alcoholic cirrhosis. Alcohol Alcohol 1998; 33: 606-8.
27. Fujimoto M, Uemura M, Nakatani Y, et al. Plasma endotoxin and serum cytokine levels in patients with alcoholic hepatitis: Relation to severity of liver disturbance. Alcohol Clin Exp Res 2000; 24: 48S-54S.
28. Parlesak A, Schafer C, Schutz T, Bode JC, Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J Hepatol 2000; 32: 742-7.
29. Urbaschek R, McCuskey RS, Rudi V, et al. Endotoxin, endotoxin-neutralizing-capacity, sCD14, sICAM-1, and cytokines in patients with various degrees of alcoholic liver disease. Alcohol Clin Exp Res 2001; 25: 261-8.
30. Rao RK, Seth A, Sheth P. Recent advances in alcoholic liver disease I. Role of intestinal permeability and endotoxemia in alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 2004; 286: G881-4.
31. Fukui H, Brauner B, Bode JC, Bode C. Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: Reevaluation with an improved chromogenic assay. J Hepatol 1991; 12: 162-9.
32. Bird GL, Sheron N, Goka J, Alexander GJ, Williams RS. Increased plasma tumor necrosis factor in severe alcoholic hepatitis. Ann Intern Med 1990; 112: 917-20.
33. Felver ME, Mezey E, McGuire M, et al. Plasma tumor necrosis factor alpha predicts decreased long-term survival in severe alcoholic hepatitis. Alcohol Clin Exp Res 1990; 14: 255-9.
34. McClain CJ, Cohen DA, Dinarello CA, Cannon JG, Shedlofsky SI, Kaplan AM. Serum interleukin-1 (IL-1) activity in alcoholic hepatitis. Life Sci 1986; 39: 1479-85.
35. Hill DB, Marsano L, Cohen D, Allen J, Shedlofsky S, McClain CJ. Increased plasma interleukin-6 concentrations in alcoholic hepatitis. J Lab Clin Med 1992; 119: 547-52.
36. Sheron N, Bird G, Koskinas J, et al. Circulating and tissue levels of the neutrophil chemotaxin interleukin-8 are elevated in severe acute alcoholic hepatitis, and tissue levels correlate with neutrophil infiltration. Hepatology 1993; 18: 41-6.
37. Nanji AA, Khettry U, Sadrzadeh SM, Yamanaka T. Severity of liver injury in experimental alcoholic liver disease. Correlation with plasma endotoxin, prostaglandin E2, leukotriene B4, and thromboxane B2. Am J Pathol 1993; 142: 367-73.
38. Keshavarzian A, Fields JZ, Vaeth J, Holmes EW. The differing effects of acute and chronic alcohol on gastric and intestinal permeability. Am J Gastroenterol 1994; 89: 2205-11.
39. Keshavarzian A, Holmes EW, Patel M, Iber F, Fields JZ, Pethkar S. Leaky gut in alcoholic cirrhosis: A possible mechanism for alcohol-induced liver damage. Am J Gastroenterol 1999; 94: 200-7.
40. Mathurin P, Deng QG, Keshavarzian A, Choudhary S, Holmes EW, Tsukamoto H. Exacerbation of alcoholic liver injury by enteral endotoxin in rats. Hepatology 2000; 32: 1008-17.
41. Nanji AA, Jokelainen K, Fotouhinia M, et al. Increased severity of alcoholic liver injury in female rats: role of oxidative stress, endotoxin, and chemokines. Am J Physiol Gastrointest Liver Physiol 2001; 281: G1348-56.
42. Schmidt KL, Henagan JM, Smith GS, Miller TA. Effects of ethanol and prostaglandin on rat gastric mucosal tight junctions. J Surg Res 1987; 43: 253-63.
43. Keshavarzian A, Choudhary S, Holmes EW, et al. Preventing gut leakiness by oats supplementation ameliorates alcohol-induced liver damage in rats. J Pharmacol Exp Ther 2001; 299: 442-8.
44. Choudhry MA, Fazal N, Goto M, Gamelli RL, Sayeed MM. Gut-associated lymphoid T cell suppression enhances bacterial translocation in alcohol and burn injury. Am J Physiol Gastrointest Liver Physiol 2002; 282: G937-47.
45. Lambert JC, Zhou Z, Wang L, Song Z, McClain CJ, Kang YJ. Prevention of alterations in intestinal permeability is involved in zinc inhibition of acute ethanol-induced liver damage in mice. J Pharmacol Exp Ther 2003; 305: 880-6.
46. Tsukamoto H, Towner SJ, Clofalo LM, French SW. Ethanol-induced liver fibrosis in rats fed high fat diet. Hepatology 1986; 6: 814-22.
47. Adachi Y, Moore LE, Bradford BU, Gao W, Thurman RG. Antibiotics prevent liver injury in rats following long-term exposure to ethanol. Gastroenterology 1995; 108: 218-24.
48. Uesugi T, Froh M, Arteel GE, et al. Role of lipopolysaccharide-binding protein in early alcohol-induced liver injury in mice. J Immunol 2002; 168: 2963-9.
49. Salaspuro M. Bacteriocolonic pathway for ethanol oxidation: characteristics and implications. Ann Med 1996; 28: 195-200.
50. Salaspuro M. Microbial metabolism of ethanol and acetaldehyde and clinical consequences. Addict Biol 1997; 2: 35-46.
51. Visapaa JP, Tillonen J, Salaspuro M. Microbes and mucosa in the regulation of intracolonic acetaldehyde concentration during ethanol challenge. Alcohol Alcohol 2002; 37: 322-6.
52. Atkinson KJ, Rao RK. Role of protein tyrosine phosphorylation in acetaldehyde-induced disruption of epithelial tight junctions. Am J Physiol Gastrointest Liver Physiol 2001; 280: G1280-8.
53. Batey R, Cao Q, Madsen G, Pang G, Russell A, Clancy R. Decreased tumor necrosis factor-α and interleukin-1α production from intrahepatic mononuclear cells in chronic ethanol consumption and upregulation by endotoxin. Alcohol Clin Exp Res 1998; 22: 150-6.
54. Kersten S, Desvergne B, Wahli W. Roles of PPARs in health and disease. Nature 2000; 405: 421-4.
55. Trifilieff A, Bench A, Hanley M, Bayley D, Campbell E, Whittaker P. PPAR-α and -γ but not -δ agonists inhibit airway inflammation in a murine model of asthma: In vitro evidence for an NF-κB-independent effect. Br J Pharmacol 2003; 139: 163-71.
56. Laszlo R Jr, Karen K, Angela D, et al. Diverse regulation of NF-κB and peroxisome proliferator-activated receptors in murine nonalcoholic fatty liver. Hepatology 2004; 40: 376-85.
57. Mandard S, Muller M, Kersten S. Peroxisome proliferator-activated receptor alpha target genes. Cell Mol Life Sci 2004; 61: 393-416.
58. Delayre-Orthez C, Becker J, Guenon I, et al. PPARα downregulates airway inflammation induced by lipopolysaccharide in the mouse. Respir Res 2005; 6: 91.
59. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ 2003; 10: 45-65.
60. Schwabe RF, Brenner DA. Mechanisms of Liver Injury. I. TNF-alpha-induced liver injury: Role of IKK, JNK, and ROS pathways. Am J Physiol Gastrointest Liver Physiol 2006; 290: G583-9.
61. Ahluwalia B, Wesley B, Adeyiga O, Smith DM, Da-Silva A, Rajguru S. Alcohol modulates cytokine secretion and synthesis in human fetus: An in vivo and in vitro study. Alcohol 2000; 21: 207-13.
62. Park P, Thakur V, Pritchard MT, McMullen MR, Nagy LE. Regulation of Kupffer cell activity during chronic ethanol exposure: Role of adiponectin. J Gastroenterol Hepatol 2006; 21: S30-3.
63. Thurman RG. II. Alcoholic liver injury involves activation of Kupffer cells by endotoxin. Am J Physiol Gastrointest Liver Physiol 1998; 275: G605-11.
64. Nagy LE. Recent insights into the role of the innate immune system in the development of alcoholic liver disease. Exp Biol Med 2003; 228: 882-90.
65. Wheeler MD, Kono H, Yin M, et al. The role of Kupffer cell oxidant production in early ethanol-induced liver disease. Free Radic Biol Med 2001; 31: 1544-9.
66. Su GL. Lipopolysaccharides in liver injury: Molecular mechanisms of Kupffer cell activation. Am J Physiol Gastrointest Liver Physiol 2002; 283: G256-65.
67. Kono H, Wheeler MD, Rusyn I, et al. Gender differences in early alcohol-induced liver injury: Role of CD14, NF-κB, and TNF-α. Am J Physiol Gastrointest Liver Physiol 2000; 278: G652-61.
68. Baud V, Karin M. Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol 2001; 11: 372-7.
69. Wheeler MD, Kono H, Yin M, et al. Delivery of the Cu/Zn-superoxide dismutase gene with adenovirus reduces early alcohol-induced liver injury in rats. Gastroenterology 2001; 120: 1241-50.
70. Su GL, Goyert SM, Fan MH, et al. Activation of human and mouse Kupffer cells by lipopolysaccharide is mediated by CD14. Am J Physiol Gastrointest Liver Physiol 2002; 283: G640-5.
71. Yin M, Wheeler MD, Kono H, et al. Essential role of tumor necrosis factor α in alcohol-induced liver injury in mice. Gastroenterology 1999; 117: 942-52.
72. Iimuro Y, Gallucci RM, Luster MI, Kono H, Thurman RG. Antibodies to tumor necrosis factor α attenuate hepatic necrosis and inflammation caused by chronic exposure to ethanol in the rat. Hepatology 1997; 26: 1530-7.
73. Nanji AA, Khettry U, Sadrzadeh SM. Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver disease. Proc Soc Exp Biol Med 1994; 205: 243-7.
74. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995; 270: 26746-9.
75. You M, Crabb DW. Recent advances in alcoholic liver disease II. Minireview: Molecular mechanisms of alcoholic fatty liver. Am J Physiol Gastrointest Liver Physiol 2004; 287: G1-6.
76. Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K. Obesity, adiponectin and vascular inflammatory disease. Curr Opin Lipidol 2003; 14: 561-6.
77. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE. The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 2001; 7: 947-53.
78. Haluzik M, Parizkova J, Haluzik MM. Adiponectin and its role in the obesity-induced insulin resistance and related complications. Physiol Res 2004; 53: 123-9.
79. Matsuzawa Y. Adiponectin: Identification, physiology and clinical relevance in metabolic and vascular disease. Atherosclerosis Supplements 2005; 6: 7-14.
80. Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003; 112: 91-100.
81. You M, Considine RV, Leone TC, Kelly DP, Crabb DW. Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice. Hepatology 2005; 42: 568-77.
82. Tsukamoto H, She H, Hazra S, Cheng J, Wang J. Fat paradox of steatohepatitis. J Gastroenterol Hepatol 2008; 23 (Suppl 1): S104-7.
83. Sierksma A, Patel H, Ouchi N, et al. Effect of moderate alcohol consumption on adiponectin, tumor necrosis factor-α, and insulin sensitivity. Diabetes Care 2004; 27: 184-9.
84. Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 2003; 423: 762-9.
85. Shklyaev S, Aslanidi G, Tennant M, et al. Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats. Proc Natl Acad Sci 2003; 100: 14217-22.
86. Yamauchi T, Nio Y, Maki T, et al. Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 2007; 13: 332-9.
87. Czaja MJ. Liver injury in the setting of steatosis: Crosstalk between adipokine and cytokine. Hepatology 2004; 40: 19-22.
88. Masaki T, Chiba S, Tatsukawa H, et al. Adiponectin protects LPS-induced liver injury through modulation of TNF-α in KK-Ay obese mice. Hepatology 2004; 40: 177-84.
89. Kitano H, Oda K, Kimura T, et al. Metabolic syndrome and robustness tradeoffs. Diabetes 2004; 53 (Suppl 3): S6-15.
90. Kamada Y, Tamura S, Kiso S, et al. Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin. Gastroenterology 2003; 125: 1796-807.
91. Ding X, Saxena NK, Lin S, Xu A, Srinivasan S, Anania FA. The roles of leptin and adiponectin: a novel paradigm in adipocytokine regulation of liver fibrosis and stellate cell biology. Am J Pathol 2005; 166: 1655-69.
92. Wang XD. Chronic alcohol intake interferes with retinoid metabolism and signaling. Nutr Rev 1999; 57: 51-9.
93. Knittel T, Kobold D, Saile B, et al. Rat liver myofibroblasts and hepatic stellate cells: Different cell populations of the fibroblast lineage with fibrogenic potential. Gastroenterology 1999; 117: 1205-21.
94. Friedman SL. Transcriptional regulation of stellate cell activation. J Gastroenterol Hepatol 2006; 21: S79-83.
95. Friedman SL, Rockey DC, Bissell DM. Hepatic fibrosis 2006: Report of the third AASLD single topic conference. Hepatology 2007; 45: 242-9.
96. Streetz K, Leifeld L, Grundmann D, et al. Tumor necrosis factor α in the pathogenesis of human and murine fulminant hepatic failure. Gastroenterology 2000; 119: 446-60.
97. Tai DI, Tsai SL, Chang YH, et al. Constitutive activation of nuclear factor κB in hepatocellular carcinoma. Cancer 2000; 89: 2274-81.
98. Tai DI, Tsai SL, Chen YM, et al. Activation of nuclear factor κB in hepatitis C virus infection: Implications for pathogenesis and hepatocarcinogenesis. Hepatology 2000; 31: 656-64.
99. Luedde T, Beraza N, Trautwein C. Evaluation of the role of nuclear factor-kappa B signaling in liver injury using genetic animal models. J Gastroenterol Hepatol 2006; 21: S43-6.
100. Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ. Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Invest 2003; 83: 655-63.
101. Platt N, da Silva RP, Gordon S. Recognizing death: the phagocytosis of apoptotic cells. Trends Cell Biol 1998; 8: 365-72.
102. Rust C, Gores GJ. Apoptosis and liver disease. Am J Med 2000; 108: 567-74.
103. Oakley F, Meso M, Iredale JP, et al. Inhibition of inhibitor of κB kinase stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis. Gastroenterology 2005; 128: 108-20.
104. Wicovsky A, Muller N, Daryab N, et al. Sustained JNK activation in response to tumor necrosis factor is mediated by caspases in a cell type-specific manner. J Biol Chem 2007; 282: 2174-83.
105. Kweon YO, Paik YH, Schnabl B, Qian T, Lemasters JJ, Brenner DA. Gliotoxin-mediated apoptosis of activated human hepatic stellate cells. J Hepatol 2003; 39: 38-46.
106. Elsharkawy AM, Oakley F, Mann DA. The role and regulation of hepatic stellate cell apoptosis in reversal of liver fibrosis. Apoptosis 2005; 10: 927-39.
107. Habens F, Srinivasan N, Oakley F, Mann DA, Ganesan A, Packham G. Novel sulfasalazine analogues with enhanced NF-κB inhibitory and apoptosis promoting activity. Apoptosis 2005; 10: 481-91.
108. Nakajima T, Wang RS, Ito Y, Aoyama T, Kamijima M. A review of hazardous chemical toxicity studies utilizing genetically-modified animals-Their application for risk assessment. Ind Health 2005; 43: 615-22.
109. Staels B, Koenig W, Habib A, et al. Activation of human aortic smooth-muscle cells is inhibited by PPARα but not by PPARγ activators. Nature 1998; 393: 790-3.
110. Marx N, Sukhova GK, Collins T, Libby P, Plutzky J. PPARα activators inhibit cytokine-induced vascular cell adhesion molecule-1 expression in human endothelial cells. Circulation 1999; 99: 3125-31.
111. Delerive P, Gervois P, Fruchart JC, Staels B. Induction of IκBα expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-α activators. J Biol Chem 2000; 275: 36703-07.
112. Fujii H. Anti-inflammatory action of PPARs. Nippon Rinsho 2005; 63: 609-15.
113. Frezza M, Surrenti C, Manzillo G, Fiaccadori F, Bortolini M, Di Padova C. Oral S-adenosylmethionine in the symptomatic treatment of intrahepatic cholestasis. A double-blind, placebo-controlled study. Gastroenterology 1990; 99: 211-5.
114. Mato JM, Camara J, Fernandez de Paz J, et al. S-adenosylmethionine in alcoholic liver cirrhosis: A randomized, placebo-controlled, double-blind, multicenter clinical trial. J Hepatol 1999; 30: 1081-9.
115. Lieber CS, Weiss DG, Groszmann R, Paronetto F, Schenker S. I. Veterans affairs cooperative study of polyenylphosphatidylcholine in alcoholic liver disease: Effects on drinking behavior by nurse/physician teams. Alcohol Clin Exp Res 2003; 27: 1757-64.
116. Lieber CS, Weiss DG, Groszmann R, Paronetto F, Schenker S. II. Veterans affairs cooperative study of polyenylphosphatidylcholine in alcoholic liver disease. Alcohol Clin Exp Res 2003; 27: 1765-72.
117. de la Maza MP, Petermann M, Bunout D, Hirsch S. Effects of long-term vitamin E supplementation in alcoholic cirrhotics. J Am Coll Nutr 1995; 14: 192-6.
118. Singh JP, Kauffman R, Bensch W, et al. Identification of a novel selective peroxisome proliferator-activated receptor α agonist, 2-methyl-2-(4-{3-[1-(4-methylbenzyl)-5-oxo-4,5-dihydro-1H-1,2,4-triazol-3-yl]propyl} phenoxy)propanoic acid (LY518674), that produces marked changes in serum lipids and apolipoprotein A-1 expression. Mol Pharmacol 2005; 68: 763-8.
119. Nissen SE, Nicholls SJ, Wolski K, et al. Effects of a potent and selective PPAR-α agonist in patients with atherogenic dyslipidemia or hypercholesterolemia: Two randomized controlled trials. JAMA 2007; 297: 1362-73.
120. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356: 2457-71.
121. Kadowaki T. Recent advances in PPARs research-Basic and clinical aspects. Nippon Rinsho 2005; 63: 539-48.
122. Tsuchida A, Yamauchi T, Takekawa S, et al. Peroxisome proliferator-activated receptor (PPAR)α activation increases adiponectin receptors and reduces obesity-related inflammation in adipose tissue: Comparison of activation of PPARα, PPARγ, and their combination. Diabetes 2005; 54: 3358-70.
123. Tsuchida A, Yamauchi T, Ito Y, et al. Insulin/Foxo1 pathway regulates expression levels of adiponectin receptors and adiponectin sensitivity. J Biol Chem 2004; 279: 30817-22.
124. Kubota N, Terauchi Y, Kubota T, et al. Pioglitazone ameliorates insulin resistance and diabetes by both adiponectin-dependent and -independent pathways. J Biol Chem 2006; 281: 8748-55.