Metabolic liver disease of obesity and role of adipose tissue in the pathogenesis of nonalcoholic fatty liver disease

World Journal of Gastroenterology

Volumn 13, Issue 26, 2007, Pages 3540-3553

  Qureshi, Kamran ^a   Abrams, Gary A ^a  

^a University of Alabama at Birmingham   (United States)

Author keywords

Adipokines; Adipose tissue; Insulin resistance; Nonalcoholic fatty liver disease; Obesity

Indexed keywords

ACYLATION STIMULATING PROTEIN; ADIPOCYTOKINE; ADIPONECTIN; ANGIOTENSINOGEN; CYTOKINE; FATTY ACID; INSULIN; INTERLEUKIN 6; LEPTIN; RESISTIN; TUMOR NECROSIS FACTOR ALPHA;

ADIPOSE TISSUE; AUTOCRINE EFFECT; CHRONIC INFLAMMATION; DIABETES MELLITUS; DISEASE ASSOCIATION; DYSLIPIDEMIA; EDITORIAL; ENDOCRINE FUNCTION; FAT INTAKE; FATTY ACID TRANSPORT; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; HYPERTENSION; IMMOBILIZATION; INSULIN RESISTANCE; LIPID METABOLISM; LIPID STORAGE; LIPODYSTROPHY; LIPOLYSIS; LIVER CIRRHOSIS; LIVER METABOLISM; METABOLIC DISORDER; MORBIDITY; MORTALITY; NONALCOHOLIC FATTY LIVER; OBESITY; PARACRINE SIGNALING; PATHOGENESIS; RISK FACTOR;

EID: 34547460043     PISSN: 10079327     EISSN: None     Source Type: Journal    
DOI: 10.3748/wjg.v13.i26.3540     Document Type: Editorial

References (202)

1. Ludwig J, Viggiano TR, McGill DB, Oh BJ. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980; 55: 434-438
2. Clark JM, Brancati FL, Diehl AM. Nonalcoholic fatty liver disease. Gastroenterology 2002; 122: 1649-1657
3. Ruhl CE, Everhart JE. Epidemiology of nonalcoholic fatty liver. Clin Liver Dis 2004; 8: 501-519, vii
4. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006; 43: S99-S112
5. Bellentani S, Tiribelli C, Saccoccio G, Sodde M, Fratti N, De Martin C, Cristianini G. Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study. Hepatology 1994; 20: 1442-1449
6. Jimba S, Nakagami T, Takahashi M, Wakamatsu T, Hirota Y, Iwamoto Y, Wasada T. Prevalence of non-alcoholic fatty liver disease and its association with impaired glucose metabolism in Japanese adults. Diabet Med 2005; 22: 1141-1145
7. Brunt EM, Janney CG, Di Bisceglie AM, Neuschwander-Tetri BA, Bacon BR. Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions. Am J Gastroenterol 1999; 94: 2467-2474
8. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference. Hepatology 2003; 37: 1202-1219
9. Skelly MM, James PD, Ryder SD. Findings on liver biopsy to investigate abnormal liver function tests in the absence of diagnostic serology. J Hepatol 2001; 35: 195-199
10. de Ledinghen V, Combes M, Trouette H, Winnock M, Amouretti M, de Mascarel A, Couzigou P. Should a liver biopsy be done in patients with subclinical chronically elevated transaminases? Eur J Gastroenterol Hepatol 2004; 16: 879-883
11. Prati D, Taioli E, Zanella A, Della Torre E, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D, Colombo M, Sirchia G. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Ann Intern Med 2002; 137: 1-10
12. Kunde SS, Lazenby AJ, Clements RH, Abrams GA. Spectrum of NAFLD and diagnostic implications of the proposed new normal range for serum ALT in obese women. Hepatology 2005; 42: 650-656
13. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A, Yeh M, McCullough AJ, Sanyal AJ. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005; 41: 1313-1321
14. Poynard T, Ratziu V, Naveau S, Thabut D, Charlotte F, Messous D, Capron D, Abella A, Massard J, Ngo Y, Munteanu M, Mercadier A, Manns M, Albrecht J. The diagnostic value of biomarkers (SteatoTest) for the prediction of liver steatosis. Comp Hepatol 2005; 4: 10
15. Ratziu V, Massard J, Charlotte F, Messous D, Imbert-Bismut F, Bonyhay L, Tahiri M, Munteanu M, Thabut D, Cadranel JF, Le Bail B, de Ledinghen V, Poynard T. Diagnostic value of biochemical markers (FibroTest-FibroSURE) for the prediction of liver fibrosis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006; 6: 6
16. Poynard T, Ratziu V, Charlotte F, Messous D, Munteanu M, Imbert-Bismut F, Massard J, Bonyhay L, Tahiri M, Thabut D, Cadranel JF, Le Bail B, de Ledinghen V. Diagnostic value of biochemical markers (NashTest) for the prediction of non alcoholo steato hepatitis in patients with non-alcoholic fatty liver disease. BMC Gastroenterol 2006; 6: 34
17. Cotrim HP, Andrade ZA, Parana R, Portugal M, Lyra LG, Freitas LA. Nonalcoholic steatohepatitis: a toxic liver disease in industrial workers. Liver 1999; 19: 299-304
18. 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 2004; 40: 1387-1395
19. Solga SF, Clark JM, Alkhuraishi AR, Torbenson M, Tabesh A, Schweitzer M, Diehl AM, Magnuson TH. Race and comorbid factors predict nonalcoholic fatty liver disease histopathology in severely obese patients. Surg Obes Relat Dis 2005; 1: 6-11
20. Willner IR, Waters B, Patil SR, Reuben A, Morelli J, Riely CA. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol 2001; 96: 2957-2961
21. Sreekumar R, Rosado B, Rasmussen D, Charlton M. Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis. Hepatology 2003; 38: 244-251
22. Diehl AM, Li ZP, Lin HZ, Yang SQ. Cytokines and the pathogenesis of non-alcoholic steatohepatitis. Gut 2005; 54: 303-306
23. Bugianesi E, McCullough AJ, Marchesini G. Insulin resistance: a metabolic pathway to chronic liver disease. Hepatology 2005; 42: 987-1000
24. Alberti KG, Zimmet P, Shaw J. The metabolic syndrome - a new worldwide definition. Lancet 2005; 366: 1059-1062
25. Poucell S, Ireton J, Valencia-Mayoral P, Downar E, Larratt L, Patterson J, Blendis L, Phillips MJ. Amiodarone-associated phospholipidosis and fibrosis of the liver. Light, immunohistochemical, and electron microscopic studies. Gastroenterology 1984; 86: 926-936
26. Grieco A, Forgione A, Miele L, Vero V, Greco AV, Gasbarrini A, Gasbarrini G. Fatty liver and drugs. Eur Rev Med Pharmacol Sci 2005; 9: 261-263
27. Pratt DS, Knox TA, Erban J. Tamoxifen-induced steatohepatitis. Ann Intern Med 1995; 123: 236
28. Novaro GM. Isoniazid and nonalcoholic steatohepatitis. J Clin Gastroenterol 1999; 28: 180
29. Blackburn GL, Mun EC. Effects of weight loss surgeries on liver disease. Semin Liver Dis 2004; 24: 371-379
30. Baddeley RM. An epilogue to jejunoileal bypass. World J Surg 1985; 9: 842-849
31. McFarland RJ, Gazet JC, Pilkington TR. A 13-year review of jejunoileal bypass. Br J Surg 1985; 72: 81-87
32. Reid AE. Nonalcoholic steatohepatitis. Gastroenterology 2001; 121: 710-723
33. Partin JS, Partin JC, Schubert WK, McAdams AJ. Liver ultrastructure in abetalipoproteinemia: Evolution of micronodular cirrhosis. Gastroenterology 1974; 67: 107-118
34. Powell EE, Searle J, Mortimer R. Steatohepatitis associated with limb lipodystrophy. Gastroenterology 1989; 97: 1022-1024
35. Fortgang IS, Belitsos PC, Chaisson RE, Moore RD. Hepatomegaly and steatosis in HIV-irifected patients receiving nucleoside analog antiretroviral therapy. Am J Gastroenterol 1995; 90: 1433-1436
36. Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA 2001; 285:2486-2497
37. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, Marks JS. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289: 76-79
38. Angulo P. Treatment of nonalcoholic fatty liver disease. Ann Hepatol 2002; 1: 12-19
39. Abrams GA, Kunde SS, Lazenby AJ, Clements RH. Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease. Hepatology 2004; 40: 475-483
40. Ratziu V, Giral P, Charlotte F, Bruckert E, Thibault V, Theodorou I, Khalil L, Turpin G, Opolon P, Poynard T. Liver fibrosis in overweight patients. Gastroenterology 2000; 118: 1117-1123
41. Ratziu V, Giral P, Charlotte F, Bruckert E, Thibault V. Theodorou I, Khalil L, Turpin G, Opolon P, Poynard T. Liver fibrosis in overweight patients. Gastroenterology 2000; 118: 1117-1123
42. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, McCullough AJ, Natale S, Forlani G, Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001; 50: 1844-1850
43. Braillon A, Capron JP, Herve MA, Degott C, Quenum C. Liver in obesity. Gut 1985; 26: 133-139
44. 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
45. Begriche K, Igoudjil A, Pessayre D, Fromenty B. Mitochondrial dysfunction in NASH: causes, consequences and possible means to prevent it. Mitochondrion 2006; 6: 1-28
46. Brautigan DL, Brown M, Grindrod S, Chinigo G, Kruszewski A, Lukasik SM, Bushweller JH, Horal M, Keller S, Tamura S, Heimark DB, Price J, Larner AN, Larner J. Allosteric activation of protein phosphatase 2C by D-chiro-inositol-galactosamine, a putative mediator mimetic of insulin action. Biochemistry 2005; 44: 11067-11073
47. Rao MS, Reddy JK. Peroxisomal beta-oxidation and steatohepatitis. Semin Liver Dis 2001; 21: 43-55
48. Fromenty B, Robin MA, Igoudjil A, Marisouri A, Pessayre D. The ins and outs of mitochondrial dysfunction in NASH. Diabetes Metab 2004; 30: 121-138
49. Horton JD, Shimomura I. Sterol regulatory element-binding proteins: activators of cholesterol and fatty acid biosynthesis. Curr Opin Lipidol 1999; 10: 143-150
50. Horton JD. Sterol regulatory element-binding proteins: transcriptional activators of lipid synthesis. Biochem Soc Trans 2002; 30: 1091-1095
51. McGarry JD, Foster DW. Effects of exogenous fatty acid concentration on glucagon-induced changes in hepatic fatty acid metabolism. Diabetes 1980; 29: 236-240
52. Yamashita H, Takenoshita M, Sakurai M, Bruick RK, Henzel WJ, Shillinglaw W, Arnot D, Uyeda K. A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver. Proc Natl Acad Sci USA 2001; 98: 9116-9121
53. Kawaguchi T, Osatomi K, Yamashita H, Kabashima T, Uyeda K. Mechanism for fatty acid "sparing" effect on glucose-induced transcription: regulation of carbohydrate-responsive element-binding protein by AMP-activated protein kinase. J Biol Chem 2002; 277: 3829-3835
54. Iizuka K, Bruick RK, Liang G, Horton JD, Uyeda K. Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis. Proc Natl Acad Sci USA 2004; 101: 7281-7286
55. Chao L, Marcus-Samuels B, Mason MM, Moitra J, Vinson C, Arioglu E, Gavrilova O, Reitman ML. Adipose tissue is required for the antidiabetic, but not for the hypolipidemic, effect of thiazolidinediones. J Clin Invest 2000; 106: 1221-1228
56. Fajas L, Schoonjans K, Gelman L, Kim JB, Najib J, Martin G, Fruchart JC, Briggs M, Spiegelman BM, Auwerx J. Regulation of peroxisome proliferator-activated receptor gamma expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1: implications for adipocyte differentiation and metabolism. Mol Cell Biol 1999; 19: 5495-5503
57. Matsusue K, Haluzik M, Lambert G, Yim SH, Gavrilova O, Ward JM, Brewer B Jr, Reitman ML, Gonzalez FJ. Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. J Clin Invest 2003; 111: 737-747
58. Kahn CR. Insulin resistance, insulin insensitivity, and insulin unresponsiveness: a necessary distinction. Metabolism 1978; 27: 1893-1902
59. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
60. Barbieri M, Ragno E, Benvenuti E, Zito GA, Corsi A, Ferrucci L, Paolisso G. New aspects of the insulin resistance syndrome: impact on haematological parameters. Diabetologia 2001; 44: 1232-1237
61. Falkner B, Sherif K, Kushner H. Gender differences in the relationship between insulin-mediated glucose utilization and sex hormones in young African-Americans. J Gend Specif Med 2000; 3: 60-65
62. Pascual E. Hyperuricemia and gout. Curr Opin Rheumatol 1994; 6: 454-458
63. Loria P, Lonardo A, Lombardini S, Carulli L, Verrone A, Ganazzi D, Rudilosso A, D'Amico R, Bertolotti M, Carulli N. Gallstone disease in non-alcoholic fatty liver: prevalence and associated factors. J Gastroenterol Hepatol 2005; 20: 1176-1184
64. Sakkinen PA, Wahl P, Cushman M, Lewis MR, Tracy RP. Clustering of procoagulation, inflammation, and fibrinolysis variables with metabolic factors in insulin resistance syndrome. Am J Epidemiol 2000; 152: 897-907
65. Yildiz BO, Yarali H, Oguz H, Bayraktar M. Glucose intolerance, insulin resistance, and hyperandrogenemia in first degree relatives of women with polycystic ovary syndrome. J Clin Endocrinol Metab 2003; 88: 2031-2036
66. Virkamaki A, Ueki K, Kahn CR. Protein-protein interaction in insulin signaling and the molecular mechanisms of insulin resistance. J Clin Invest 1999; 103: 931-943
67. Previs SF, Withers DJ, Ren JM, White MF, Shulman GI. Contrasting effects of IRS-1 versus IRS-2 gene disruption on carbohydrate and lipid metabolism in vivo. J Biol Chem 2000; 275: 38990-38994
68. DeFronzo RA, Tobin JD, Andrea R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214-E223
69. Morino K, Petersen KF, Shulman GI. Molecular mechanisms of insulin resistance in humans and their potential links with mitochondrial dysfunction. Diabetes 2006; 55 Suppl 2: S9-S15
70. Unger RH. Lipid overload and overflow: metabolic trauma and the metabolic syndrome. Trends Endocrinol Metab 2003; 14: 398-403
71. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Forlani G, Melchionda N. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999; 107: 450-455
72. Forouhi NG, Jenkinson G, Thomas EL, Mullick S, Mierisova S, Bhonsle U, McKeigue PM, Bell JD. Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men. Diabetologia 1999; 42: 932-935
73. Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia 1999; 42: 113-116
74. Reaven G. The metabolic syndrome or the insulin resistance syndrome? Different names, different concepts, and different goals. Endocrinol Metab Clin North Am 2004; 33: 283-303
75. Hegele RA. Phenomics, lipodystrophy, and the metabolic syndrome. Trends Cardiovasc Med 2004; 14: 133-137
76. 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: 103-107
77. Day CP, James OF. Steatohepatitis: a tale of two "hits"? Gastroenterology 1998; 114: 842-845
78. Perseghin G, Petersen K, Shulman GI. Cellular mechanism of insulin resistance: potential links with inflammation. Int J Obes Relat Metab Disord 2003; 27 Suppl 3: S6-S11
79. Combettes-Souverain M, Issad T. Molecular basis of insulin action. Diabetes Metab 1998; 24: 477-489
80. McCullough AJ. Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 2006; 40: S17-S29
81. Sies H, Stahl W, Sevanian A. Nutritional, dietary and postprandial oxidative stress. J Nutr 2005; 135: 969-972
82. Aronis A, Madar Z, Tirosh O. Mechanism underlying oxidative stress-mediated lipotoxicity: exposure of J774.2 macrophages to triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis. Free Radic Biol Med 2005; 38: 1221-1230
83. Videla LA, Rodrigo R, Orellana M, Fernandez V, Tapia G, Quinones L, Varela N, Contreras J, Lazarte R, Csendes A, Rojas J, Maluenda F, Burdiles P, Diaz JC, Smok C, Thielemann L, Poniachik J. Oxidative stress-related parameters in the liver of non-alcoholic fatty liver disease patients. Clin Sci (Lond) 2004; 106: 261-268
84. Poniachik J, Csendes A, Diaz JC, Rojas J, Burdiles P, Maluenda F, Smok G, Rodrigo R, Videla LA. Increased production of IL-1alpha and TNF-alpha in lipopolysaccharide-stimulated blood from obese patients with non-alcoholic fatty liver disease. Cytokine 2006; 33: 252-257
85. Schattenberg JM, Wang Y, Singh R, Rigoli RM, Czaja MJ. Hepatocyte CYP2E1 overexpression and steatohepatitis lead to impaired hepatic insulin signaling. J Biol Chem 2005; 280: 9887-9894
86. De Craemer D, Pauwels M, Van den Branden C. Alterations of peroxisomes in steatosis of the human liver: a quantitative study. Hepatology 1995; 22: 744-752
87. Lombardo YB, Chicco AG. Effects of dietary polyunsaturated n-3 fatty acids on dyslipidemia and insulin resistance in rodents and humans. A review. J Nutr Biochem 2006; 17: 1-13
88. Woodcroft KJ, Hafner MS, Novak RF. Insulin signaling in the transcriptional and posttranscriptional regulation of CYP2E1 expression. Hepatology 2002; 35: 263-273
89. Hotamisligil GS. Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes. Diabetes 2005; 54 Suppl 2: S73-S78
90. Mathurin P, Gonzalez F, Kerdraon O, Leteurtre E, Arnalsteen L, Hollebecque A, Louvet A, Dharancy S, Cocq P, Jany T, Boitard J, Deltenre P, Romon M, Pattou F. The evolution of severe steatosis after bariatric surgery is related to insulin resistance. Gastroenterology 2006; 130: 1617-1624
91. Von Gierke E, Ueber fett metabolism. Var Deutsch Ges Path 1906; 10: 182-185
92. Ahima RS. Adipose tissue as an endocrine organ. Obesity (Silver Spring) 2006; 14 Suppl 5: 242S-249S
93. Zierath JR, Livingston JN, Thorne A, Bounder J, Reynisdottir S, Lonnqvist F, Arner P. Regional difference in insulin inhibition of non-esterified fatty acid release from human adipocytes: relation to insulin receptor phosphorylation and intracellular signalling through the insulin receptor substrate-1 pathway. Diabetologia 1998; 41: 1343-1354
94. Wu X, Hoffstedt J, Deeb W, Singh R, Sedkova N, Zilbering A, Zhu L, Park PK, Arner P, Goldstein BJ. Depot-specific variation in protein-tyrosine phosphatase activities in human omental and subcutaneous adipose tissue: a potential contribution to differential insulin sensitivity. J Clin Endocrinol Metab 2001; 86: 5973-5980
95. van der Kooy K, Leenen R, Seidell JC, Deurenberg P, Visser M. Abdominal diameters as indicators of visceral fat: comparison between magnetic resonance imaging and anthropometry. Br J Nutr 1993; 70: 47-58
96. Iacobellis G. Imaging of visceral adipose tissue: an emerging diagnostic tool and therapeutic target. Curr Drug Targets Cardiovasc Haematol Disord 2005; 5: 345-353
97. Grimble RF. Inflammatory status and insulin resistance. Curr Opin Clin Nutr Metab Care 2002; 5: 551-559
98. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004; 89: 2548-2556
99. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004; 145: 2273-2282
100. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004; 92: 347-355
101. Krug AW, Ehrhart-Bornstein M. Newly discovered endocrine functions of white adipose tissue: possible relevance in obesity-related diseases. Cell Mol Life Sci 2005; 62: 1359-1362
102. Nielsen S, Guo Z, Johnson CM, Hensrud DD, Jensen MD. Splanchnic lipolysis in human obesity. J Clin Invest 2004; 113: 1582-1588
103. Randle PJ, Garland PB, Hales CN, Newsholme EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet 1963; 1: 785-789
104. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest 2000; 106: 473-481
105. Thomas EL, Hamilton G, Patel N, O'Dwyer R, Dore CJ, Goldin RD, Bell JD, Taylor-Robinson SD. Hepatic triglyceride content and its relation to body adiposity: a magnetic resonance imaging and proton magnetic resonance spectroscopy study. Gut 2005; 54: 122-127
106. de Almeida IT, Cortez-Pinto H, Fidalgo G, Rodrigues D, Camilo ME. Plasma total and free fatty acids composition in human non-alcoholic steatohepatitis. Clin Nutr 2002; 21: 219-223
107. Carey DG, Jenkins AB, Campbell LV, Freund J, Chisholm DJ. Abdominal fat and insulin resistance in normal and overweight women: Direct measurements reveal a strong relationship in subjects at both low and high risk of NIDDM. Diabetes 1996; 45: 633-638
108. Roden M. Non-invasive studies of glycogen metabolism in human skeletal muscle using nuclear magnetic resonance spectroscopy. Curr Opin Clin Nutr Metab Care 2001; 4: 261-266
109. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-432
110. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763-770
111. Ahima RS, Saper CB, Flier JS, Elmquist JK. Leptin regulation of neuroendocrine systems. Front Neuroendocrinol 2000; 21: 263-307
112. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334: 292-295
113. Corica F, Allegra A, Corsonello A, Buemi M, Calapai G, Ruello A, Nicita Mauro V, Ceruso D. Relationship between plasma leptin levels and the tumor necrosis factor-alpha system in obese subjects. Int J Obes Relat Metab Disord 1999; 23: 355-360
114. Ahren B, Baldwin RM, Havel PJ. Pharmacokinetics of human leptin in mice and rhesus monkeys. Int J Obes Relat Metab Disord 2000; 24: 1579-1585
115. Wellhoener P, Fruehwald-Schultes B, Kern W, Dantz D, Kerner W, Born J, Fehm HL, Peters A. Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans. J Clin Endocrinol Metab 2000; 85: 1267-1271
116. Mayer-Davis EJ, D'Agostino R Jr, Karter AJ, Haffner SM, Rewers MJ, Saad M, Bergman RN. Intensity and amount of physical activity in relation to insulin sensitivity: the Insulin Resistance Atherosclerosis Study. JAMA 1998; 279: 669-674
117. Dubuc GR, Phinney SD, Stern JS, Havel PJ. Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism 1998; 47: 429-434
118. Boden G, Chen X, Mozzoli M, Ryan I. Effect of fasting on serum leptin in normal human subjects. J Clin Endocrinol Metab 1996; 81: 3419-3423
119. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O'Rahilly S. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002; 110: 1093-1103
120. Muoio DM, Dohm GL, Fiedorek FT Jr, Tapscott EB, Coleman RA. Leptin directly alters lipid partitioning in skeletal muscle. Diabetes 1997; 46: 1360-1363
121. Minokoshi Y, Kim YB, Peroni OD, Fryer LG, Muller C, Caning D, Kahn BB. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002; 415: 339-343
122. Kaplan ML, Leveille GA. Obesity: prediction of preabesity among progeny from crosses of ob+ mice. Proc Soc Exp Biol Med 1973; 143: 925-928
123. Tartaglia LA, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards GJ, Campfield LA, Clark FT, Deeds J, Muir C, Sanker S, Moriarty A, Moore KJ, Smutko JS, Mays GG, Wool EA, Monroe CA, Tepper RI. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995; 83: 1263-1271
124. Ebihara K, Kusakabe T, Hirata M, Masuzaki H, Miyanaga F, Kobayashi N, Tanaka T, Chusho H, Miyazawa T, Hayashi T, Hosoda K, Ogawa Y, DePaoli AM, Fukushima M, Nakao K. Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab 2007; 92: 532-541
125. Danforth E Jr. Failure of adipocyte differentiation causes type II diabetes mellitus? Nat Genet 2000; 26: 13
126. Lee JH, Chan JL, Sourlas E, Raptopoulos V, Mantzoros CS. Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy. J Clin Endocrinol Metab 2006; 91: 2605-2611
127. Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 2002; 26: 1407-1433
128. Caro JF, Kolaczynski JW, Nyce MR, Ohannesian JP, Opentanova I, Goldman WH, Lynn RB, Zhang PL, Sinha MK, Considine RV. Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance. Lancet 1996; 348: 159-161
129. Wang Z, Thou YT, Kakuma T, Lee Y, Kalra SP, Kalra PS, Pan W, Unger RH. Leptin resistance of adipocytes in obesity: role of suppressors of cytokine signaling. Biochem Biophys Res Commun 2000; 277: 20-26
130. Honda H, Ikejima K, Hirose M, Yoshikawa M, Lang T, Enomoto N, Kitamura T, Takei Y, Sato N. Leptin is required for fibrogenic responses induced by thioacetamide in the murine liver. Hepatology 2002; 36: 12-21
131. Saxena NK, Saliba G, Floyd JJ, Anania FA. Leptin induces increased alpha2(I) collagen gene expression in cultured rat hepatic stellate cells. J Cell Biochem 2003; 89: 311-320
132. Ikejima K, Takei Y, Honda H, Hirose M, Yoshikawa M, Zhang YJ, Lang T, Fukuda T, Yamashina S, Kitamura T, Sato N. Leptin receptor-mediated signaling regulates hepatic fibrogenesis and remodeling of extracellular matrix in the rat. Gastroenterology 2002; 122: 1399-410
133. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to Clq, produced exclusively in adipocytes. J Biol Chem 1995; 270: 26746-26749
134. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996; 271: 10697-10703
135. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79-83
136. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930-1935
137. Statnick MA, Beavers LS, Conner LJ, Corominola H, Johnson D, Hammond CD, Rafaeloff-Phail R, Seng T, Suter TM, Sluka JP, Ravussin E, Gadski RA, Caro JF. Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes. Int J Exp Diabetes Res 2000; 1: 81-88
138. Krakoff J, Funahashi T, Stehouwer CD, Schalkwijk CG, Tanaka S, Matsuzawa Y, Kobes S, Tataranni PA, Hanson RL, Knowler WC, Lindsay RS. Inflammatory markers, adiponectin, and risk of type 2 diabetes in the Pima Indian. Diabetes Care 2003; 26: 1745-1751
139. Louthan MV, Barve S, McClain CJ, Joshi-Barve S. Decreased serum adiponectin: an early event in pediatric nonalcoholic fatty liver disease. J Pediatr 2005; 147: 835-882
140. Ruan H, Hacohen N, Golub TR, Van Parijs L, Lodish HF. Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes 2002; 51: 1319-1336
141. Matsuzawa Y, Funahashi T, Nakamura T. Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances. Ann N Y Acad Sci 1999; 892: 146-154
142. Kadowaki T, Hara K, Yamauchi T, Terauchi Y, Tobe K, Nagai R. Molecular mechanism of insulin resistance and obesity. Exp Biol Med (Maywood) 2003; 228: 1111-1117
143. 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
144. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7: 941-946
145. Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 2001; 98: 2005-2010
146. Lopez-Bermejo A, Botas P, Funahashi T, Delgado E, Kihara S, Ricart W, Fernandez-Real JM. Adiponectin, hepatocellular dysfunction and insulin sensitivity. Clin Endocrinol (Oxf) 2004; 60: 256-263
147. Kamada Y, Tamura S, Kiso S, Matsumoto H, Saji Y, Yoshida Y, Fukui K, Maeda N, Nishizawa H, Nagaretani H, Okamoto Y, Kihara S, Miyagawa J, Shinomura Y, Funahashi T, Matsuzawa Y. Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin. Gastroenterology 2003; 125: 1796-1807
148. Xu A, Yin S, Wong L, Chan KW, Lam KS. Adiponectin ameliorates dyslipidemia induced by the human immunodeficiency virus protease inhibitor ritonavir in mice. Endocrinology 2004; 145: 487-494
149. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259: 87-91
150. Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB. The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 1995; 95: 2111-2119
151. Van der Poll T, Romijn JA, Endert E, Borm JJ, Buller HR, Sauerwein HP. Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. Am J Physiol 1991; 261: E457-E465
152. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 1996; 271: 665-668
153. Panagiotakos DB, Pitsavos C, Yannakoulia M, Chrysohoou C, Stefanadis C. The implication of obesity and central fat on markers of chronic inflammation: The ATTICA study. Atherosclerosis 2005; 183: 308-315
154. Ofei F, Hurel S, Newkirk J, Sopwith M, Taylor R. Effects of an engineered human anti-TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 1996; 45: 881-885
155. Papanicolaou DA, Vgontzas AN. Interleukin-6: the endocrine cytokine. J Clin Endocrinol Metab 2000; 85: 1331-1333
156. Ridker PM, Rifai N, Stampfer MJ, Hennekens CH. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 2000; 101: 1767-1772
157. Spranger J, Kroke A, Mohlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF. Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Diabetes 2003; 52: 812-817
158. Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin-6 induces cellular insulin resistance in hepatocytes. Diabetes 2002; 51: 3391-3399
159. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307-312
160. Patel L, Buckels AC, Kinghom IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 2003; 300: 472-476
161. Stejskal D, Adamovska S, Bartek J, Jurakova R, Proskova J. Resistin-concentrations in persons with type 2 diabetes mellitus and in individuals with acute inflammatory disease. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2003; 147: 63-69
162. Janowska J, Zahorska-Markiewicz B, Olszanecka-Glinianowicz M. Relationship between serum resistin concentration and proinflammatory cytokines in obese women with impaired and normal glucose tolerance. Metabolism 2006; 55: 1495-1499
163. Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BL, Murphy LJ.
164. Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001; 414: 799-806
165. Banerjee RR, Rangwala SM, Shapiro JS, Rich AS, Rhoades B, Qi Y, Wang J, Rajala MW, Pocai A, Scherer PE, Steppan CM, Ahima RS, Obici S, Rossetti L, Lazar MA. Regulation of fasted blood glucose by resistin. Science 2004; 303: 1195-1198
166. Way JM, Gorgun CZ, Tong Q, Uysal KT, Brown KK, Harrington WW, Oliver WR Jr, Willson TM, Kliewer SA, Hotamisligil GS. Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor gamma agonists. J Biol Chem 2001; 276: 25651-25653
167. Xia Z, Cianflone K. Acylation-stimulating protein precursor proteins in adipose tissue in human obesity. Metabolism 2003; 52: 1360-1366
168. Maslowska M, Sniderman AD, Germinanio R, Cianflone K. ASP stimulates glucose transport in cultured human adipocytes. Int J Obes Relat Metab Disord 1997; 21: 261-266
169. Cianflone K, Xia Z, Chen LY. Critical review of acylation-stimulating protein physiology in humans and rodents. Biochim Biophys Acta 2003; 1609: 127-143
170. Maslowska M, Scantlebury T, Germinario R, Cianflone K. Acute in vitro production of acylation stimulating protein in differentiated human adipocytes. J Lipid Res 1997; 38: 1-11
171. Saleh J, Christou N, Cianflone K. Regional specificity of ASP binding in human adipose tissue. Am J Physiol 1999; 276: E815-E821
172. Massiera F, Bloch-Faure M, Ceiler D, Murakami K, Fukamizu A, Gasc JM, Quignard-Boulange A, Negrel R, Ailhaud G, Seydoux J, Meneton P, Teboul M. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J 2001; 15: 2727-2729
173. Umemura S, Nyui N, Tamura K, Hibi K, Yamaguchi S, Nakamaru M, Ishigami T, Yabana M, Kihara M, Inoue S, Ishii M. Plasma angiotensinogen concentrations in obese patients. Am J Hypertens 1997; 10: 629-633
174. Dixon JB, Bhathal PS, Jonsson JR, Dixon AF, Powell EE, O'Brien PE. Pro-fibrotic polymorphisms predictive of advanced liver fibrosis in the severely obese. J Hepatol 2003; 39: 967-971
175. Reitman ML, Arioglu E, Gavrilova O, Taylor SI. Lipoatrophy revisited. Trends Endocrinol Metab 2000; 11: 410-416
176. Gavrilova O, Marcus-Samuels B, Graham D, Kim JK, Shulman GI, Castle AL, Vinson C, Eckhaus M, Reitman ML. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest 2000; 105: 271-278
177. Addy CL, Gavrila A, Tsiodras S, Brodovicz K, Karchmer AW, Mantzoros CS. Hypoadiponectinemia is associated with insulin resistance, hypertriglyceridemia, and fat redistribution in human immunodeficiency virus-infected patients treated with highly active antiretroviral therapy. J Clin Endocrinol Metab 2003; 88: 627-636
178. Reue K, Phan J. Metabolic consequences of lipodystrophy in mouse models. Curr Opin Clin Nutr Metab Care 2006; 9: 436-441
179. Estrada V, Martinez-Larrad MT, Gonzalez-Sanchez JL, de Villar NG, Zabena C, Fernandez C, Serrano-Rios M. Lipodystrophy and metabolic syndrome in HIV-infected patients treated with antiretroviral therapy. Metabolism 2006; 55: 940-945
180. Wolfsdorf J, Sadeghi-Nejad A, Senior B. Leptin-replacement therapy in lipodystrophy. N Engl J Med 2002; 346: 2008-2009; author reply 2009-2010
181. Clark JM, Diehl AM. Nonalcoholic fatty liver disease: an underrecognized cause of cryptogenic cirrhosis. JAMA 2003; 289: 3000-3004
182. Caldwell SH, Oelsner DH, Iezzoni JC, Hespenheide EE, Battle EH, Driscoll CJ. Cryptogenic cirrhosis: clinical characterization and risk factors for underlying disease. Hepatology 1999; 29: 664-669
183. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, Rizzetto M. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002; 123: 134-140
184. Ekstedt M, Franzen LE, Mathiesen UL, Thorelius L, Holmqvist M, Bodemar G, Kechagias S. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865-873
185. Fassio E, Alvarez E, Dominguez N, Landeira G, Longo C. Natural history of nonalcoholic steatohepatitis: a longitudinal study of repeat liver biopsies. Hepatology 2004; 40: 820-826
186. Musso G, Gambino R, De Michieli F, Cassader M, Rizzetto M, Durazzo M, Faga E, Silli B, Pagano G. Dietary habits and their relations to insulin resistance and postprandial lipemia in nonalcoholic steatohepatitis. Hepatology 2003; 37: 909-916
187. Wigg AJ, Roberts-Thomson IC, Dymock RB, McCarthy PJ, Grose RH, Cummins AG. The role of small intestinal bacterial overgrowth, intestinal permeability, endotoxaemia, and tumour necrosis factor alpha in the pathogenesis of non-alcoholic steatohepatitis. Gut 2001; 48: 206-211
188. Singh H, Pollock R, Uhanova J, Kryger M, Hawkins K, Minuk GY. Symptoms of obstructive sleep apnea in patients with nonalcoholic fatty liver disease. Dig Dis Sci 2005; 50: 2338-2343
189. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356-1362
190. Dixon JB, Bhathal PS, O'Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology 2001; 121: 91-100
191. Cassiman D, Libbrecht L, Desmet V, Denef C, Roskams T. Hepatic stellate cell/myofibroblast subpopulations in fibrotic human and rat livers. J Hepatol 2002; 36: 200-209
192. Reeves HL, Friedman SL. Activation of hepatic stellate cells - a key issue in liver fibrosis. Front Biosci 2002; 7: d808-d826
193. Bugianesi E, Manzini P, D'Antico S, Vanni E, Longo F, Leone N, Massarenti P, Piga A, Marchesini G, Rizzetto M. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology 2004; 39: 179-187
194. Svegliati-Baroni G, Ridolfi F, Di Sario A, Casini A, Marucci L, Gaggiotti G, Orlandoni P, Macarri G, Perego L, Benedetti A, Folli F. Insulin and insulin-like growth factor-1 stimulate proliferation and type I collagen accumulation by human hepatic stellate cells: differential effects on signal transduction pathways. Hepatology 1999; 29: 1743-1751
195. Paradis V, Perlemuter G, Bonvoust F, Dargere D, Parfait B, Vidaud M, Conti M, Huet S, Ba N, Buffet C, Bedossa P. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology 2001; 34: 738-744
196. Parola M, Robino G. Oxidative stress-related molecules and liver fibrosis. J Hepatol 2001; 35: 297-306
197. Aleffi S, Petrai I, Bertolani C, Parola M, Colombatto S, Novo E, Vizzutti F, Anania FA, Milani S, Rombouts K, Laffi G, Pinzani M, Marra F. Upregulation of proinflammatory and proangiogenic cytokines by leptin in human hepatic stellate cells. Hepatology 2005; 42: 1339-1348
198. Meier U, Gressner AM. Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 2004; 50: 1511-1525
199. Leu JI, Crissey MA, Taub R. Massive hepatic apoptosis associated with TGF-beta1 activation after Fas ligand treatment of IGF binding protein-1-deficient mice. J Clin Invest 2003; 111: 129-139
200. Jansson PA, Larsson A, Lonnroth PN. Relationship between blood pressure, metabolic variables and blood flow in obese subjects with or without non-insulin-dependent diabetes mellitus. Eur J Clin Invest 1998; 28: 813-818
201. Straczkowski M, Dzienis-Straczkowska S, Stepien A, Kowalska I, Szelachowska M, Kinalska I. Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. J Clin Endocrinol Metab 2002; 87: 4602-4606
202. De Pergola G, De Mitrio V, Giorgino F, Sciaraffia M, Minenna A, Di Bari L, Pannacciulli N, Giorgino R. Increase in both pro-thrombotic and anti-thrombotic factors in obese premenopausal women: relationship with body fat distribution. Int J Obes Relat Metab Disord 1997; 21: 527-535