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References

  • 1
    Barrett PV, Mullins FX, Berlin NI. Studies on the biosynthetic production of bilirubin-C14: an improved method utilizing delta-aminolevulinic acid-4-C14 in dogs. J Lab Clin Med 1966; 68: 905912.
  • 2
    Barrett PVD, Berk PD, Menken M, Berlin NI. Bilirubin turnover studies in normal and pathologic states using bilirubin-14C. Ann Intern Med 1968; 68: 355377.
  • 3
    Berk PD, Howe RB, Bloomer JR, Berlin NI. Studies of bilirubin kinetics in normal adults. J Clin Invest 1969; 48: 21762190.
  • 4
    Bloomer JR, Berk PD, Howe RB, Waggoner JG, Berlin NI. Comparison of fecal urobilinogen excretion with bilirubin production in normal volunteers and patients with increased bilirubin production. Clin Chim Acta 1970; 29: 463471.
  • 5
    Berk PD, Rodkey FL, Blaschke TF, Collison HA, Waggoner JG. Comparison of plasma bilirubin turnover and carbon monoxide production in man. J Lab Clin Med 1974; 83: 2937.
  • 6
    Howe RB, Berlin NI, Berk PD. Estimation of bilirubin production in man. In: The Chemistry and Physiology of Bile Pigments. Berk PD, Berlin NI, Eds. Washington, DC: U.S. Department of Health, Education and Welfare/U.S. Government Printing Office; 1977.
  • 7
    Berk PD, Bloomer RJ, Howe RB, Blaschke TF, Berlin NI. Bilirubin production as a measure of red cell life span. J Lab Clin Med 1972; 79: 364378.
  • 8
    Berlin NI, Berk PD. Quantitative aspects of bilirubin metabolism for hematologists: a review. Blood 1981; 57: 983999.
  • 9
    Berk PD, Berman MD, Blitzer BL, Chretien P, Martin JF, Scharschmidt BF, et al. Effect of splenectomy on hepatic bilirubin clearance in patients with hereditary spherocytosis: Implications for the diagnosis of Gilbert's syndrome. J Lab Clin Med 1981; 98: 3745.
  • 10
    Berk PD, Martin JF, Blaschke TF, Scharschmidt BF, Plotz PH. Unconjugated hyperbilirubinemia: physiologic evaluation and experimental approaches to therapy. Ann Intern Med 1975; 82: 552570.
  • 11
    Korenblat K, Berk PD. Hyperbilirubinemia in the setting of anti-viral therapy. Clin Gastroenterol Hepatol 2005; 3: 303310.
  • 12
    Jones EA, Carson ER, Berk PD. The role of kinetic analysis and mathematical modeling in the study of bilirubin metabolism in vivo. In: Bilirubin, Vol. II. Metabolism. Heirwegh KPM, Brown SB, Eds. Boca Raton, FL: CRC Press; 1982: 133172.
  • 13
    Jones EA, Carson ER, Berk PD. Quantitation of bilirubin metabolism in vivo: kinetic studies and mathematical modeling. In: Ostrow JD, Ed. Bilirubin, Bile Pigments and Jaundice. New York, NY: Marcel Dekker; 1986: 439474.
  • 14
    Berk PD, Bloomer JR, Howe RB, Berlin NI. Constitutional hepatic dysfunction (Gilbert's syndrome): a new definition based on kinetic studies with unconjugated radio bilirubin. Am J Med 1970; 49: 296305.
  • 15
    Bloomer JR, Berk PD, Howe RB, Berlin NI. Bilirubin metabolism in congenital non-hemolytic jaundice. Pediatr Res 1971; 5: 256274.
  • 16
    Blaschke TF, Berk PD, Scharschmidt BF, Guyther JR, Vergalla JM, Waggoner JG. Crigler-Najjar Syndrome: An unusual course with development of neurologic damage at age 18. Pediatr Res 1974; 8: 573590.
  • 17
    Berk PD, Scharschmidt BF, Waggoner JG, White SC: The effect of repeated phlebotomy on bilirubin turnover, bilirubin clearance and unconjugated hyperbilirubinemia in the Crigler-Najjar syndrome and the jaundiced Gunn rat: Application of computers to experimental design. Clin Sci Mol Med 1976; 50: 333348.
  • 18
    Bloomer JR, Berk PD, Howe RB. Hepatic clearance of unconjugated bilirubin in cholestatic liver diseases. Am J Dig Dis 1974; 19: 914.
  • 19
    Berk PD, Javitt N. Hyperbilirubinemia and cholestasis. Am J Med 1978; 64: 311326.
  • 20
    Summerfield JA, Scott J, Berman M, Cameron G, Bloomer JR, Berk PD, et al. Benign recurrent intrahepatic cholestasis: Studies of bilirubin kinetics, bile acids, and cholangiography. Gut 1980; 21: 154160.
  • 21
    Jones EA, Shrager R, Bloomer JR, Berk PD, Howe RB, Berlin NI. Quantitative studies of the delivery of hepatic synthesized bilirubin to plasma utilizing aminolevulinic acid 4-14C and bilirubin-3H in man. J Clin Invest 1972; 51: 24502458.
  • 22
    Gisselbrecht C, Berk PD. Failure of phenobarbital to increase bilirubin production in the rat. Biochem Pharm 1974; 23: 28952905.
  • 23
    Berk PD, Blaschke TF, Scharschmidt BF, Waggoner JG, Berlin NI. A new approach to quantitation of the various sources of bilirubin in man. J Lab Clin Med 1976; 87: 767780.
  • 24
    Jones EA, Bloomer JR, Berk PD, Carson ER, Owens D, Berlin NI. Quantitation of hepatic bilirubin synthesis in man. In: The Chemistry and Physiology of Bile Pigments. Berk PD, Berlin NI, Eds. Washington, DC: U.S. Department of Health, Education and Welfare/U.S. Government Printing Office; 1977: 189205.
  • 25
    Blaschke TF, Berk PD: A new approach to estimation of early labeled peak bilirubin synthesis in man. In: The Chemistry and Physiology of Bile Pigments. Berk PD, Berlin NI, Eds. Washington, DC: U.S. Department of Health, Education and Welfare/U.S. Government Printing Office; 1977: 206215.
  • 26
    Okuda H, Tavoloni N, Blaschke TF, Kiang CL, Jones MJT, Waggoner JG, Sardana MK, Sassa S, Shrager RI, Berk PD: Phenobarbital does not increase early labelling of bilirubin from 4-[14C]- aminolevulinic acid in man and rat. HEPATOLOGY 1991; 14: 11531160.
  • 27
    Vierling JM, Berk PD, Hofmann AF, Martin JF, Wolkoff AW, Scharschmidt BF. Normal fasting state levels of serum cholyl conjugated bile acids in Gilbert's syndrome: An aid to the diagnosis. HEPATOLOGY 1982; 2: 340343.
  • 28
    Blaschke TF, Berk PD, Rodkey FL, Scharschmidt BF, Collison HA, Waggoner JG. Drugs and the liver. I. Effects of glutethimide and phenobarbital on hepatic bilirubin clearance, plasma bilirubin turnover and carbon monoxide production in man. Biochem Pharm 1974; 23: 27952806.
  • 29
    Sherlock S. Diseases of the Liver and Biliary System. 8th Ed. London, UK: Blackwell; 1989: 241243.
  • 30
    Blanckaert N, Schmid R. Physiology and pathophysiology of bilirubin metabolism. In: Zakim D, Boyer TD, Eds. Hepatology. Philadelphia, PA: W.B. Saunders; 1982: Chapter 10.
  • 31
    Robertson KJ, Clarke D, Sutherland L, Wooster R, Coughtrie MW, Burchell B. Investigation of the molecular basis of the genetic deficiency of UDP-glucuronosyltransferase in Crigler-Najjar syndrome. J Inherit Metab Dis 1991; 14: 563579.
  • 32
    Bosma PJ, Chowdhury NR, Goldhoorn BG, Hofker MH, Oude Elferink RPJ, Jansen PL, et al. Sequence of exons and the flanking regions of human bilirubin-UDP-glucuronosyltransferase gene complex and identification of a genetic mutation in a patient with Crigler-Najjar syndrome, type I. HEPATOLOGY 1992; 15: 941947.
  • 33
    Ritter JK, Chen F, Sheen YY, Tran HM, Kimura S, Yeatman MT, et al. A novel complex locus UGT1 encodes human bilirubin, phenol, and other UDP-glucuronosyltransferase isozymes with identical carboxyl termini. J Biol Chem 1992; 267: 32573261.
  • 34
    Bosma PJ, Seppen J, Goldhoorn B, Bakker C, Oude Elferink RPJ, Chowdhury JR, et al. Bilirubin UDP-glucuronosyltransferase 1 is the only relevant bilirubin glucuronidating isoform in man. J Biol Chem 1994; 269: 1796017964.
  • 35
    Burchell B, Hume R. Molecular genetic basis of Gilbert's syndrome. J Gastroenterol Hepatol 1999; 14: 960966.
  • 36
    Bosma PJ. Inherited disorders of bilirubin metabolism. J Hepatol 2003; 38: 107117.
  • 37
    Scharschmidt BF, Waggoner JG, Berk PD. Hepatic organic anion uptake in the rat. J Clin Invest 1975; 56: 12801292.
  • 38
    Reichen J, Berk PD. Isolation of an organic anion binding protein from rat liver plasma membrane fractions by affinity chromatography. Biochem Biophys Res Commun 1979; 91: 484489.
  • 39
    Stremmel W, Gerber MD, Glezerov V, Thung SN, Kochwa S, Berk PD. Physicochemical and immuno-histological studies of a sulfobromopthalein and bilirubin binding protein from rat liver plasma membranes. J Clin Invest 1983; 71: 17961805.
  • 40
    Stremmel W, Berk PD. Hepatocellular uptake of sulfobromophthalein (BSP) and bilirubin is selectively inhibited by an antibody to the liver plasma membrane BSP/bilirubin binding protein. J Clin Invest 1986; 78: 822826.
  • 41
    Briz O, Serrano MA, MacIas RI, Gonzalez-Gallego J, Marin JJ. Role of organic anion-transporting polypeptides, OATP-A, OATP-C and OATP-8, in the human placenta-maternal liver tandem excretory pathway for foetal bilirubin. Biochem J 2003; 371(Pt 3): 897905.
  • 42
    Cui Y, König J, Leier I, Buchholz U, Keppler D. Hepatic uptake of bilirubin and its conjugates by the human organic anion transporter SLC21A6. J Biol Chem 2001; 276: 96269630.
  • 43
    Wang P, Kim RB, Chowdhury JR, Wolkoff AW. The human organic anion transport protein SLC21A6 is not sufficient for bilirubin transport. J Biol Chem 2003; 278: 2069520699.
  • 44
    Bloomer JR, Berk PD, Vergalla J, Berlin NI. Influence of albumin on the hepatic uptake of unconjugated bilirubin. Clin Sci 1973; 45: 505516.
  • 45
    Bloomer JR, Berk PD, Vergalla J, Berlin NI. Influence of albumin on the extravascular distribution of unconjugated bilirubin. Clin Sci 1973; 45: 517526.
  • 46
    Weisiger R, Gollan J, Ockner R. Receptor for albumin on the liver cell surface may mediate uptake of fatty acids and other albumin-bound substances Science 1981; 211: 10481051.
  • 47
    Weisiger R, Gollan J, Ockner R. An albumin receptor on the liver cell may mediate hepatic uptake of sulfobromphthalein and bilirubin; bound ligand, not free, is the major uptake determinant [Abstract]. Gastroenterology 1980; 79: 1065.
  • 48
    Nunes R, Kiang CL, Berk PD. “Albumin receptor” uptake kinetics do not require an intact lobular architecture and are not specific for albumin. J Hepatol 1988; 7: 293304.
  • 49
    Nunes RM, Isola LM, Sorrentino D, Berk PD. Oleate uptake by isolated hepatocytes consists of two components, each driven by the unbound oleate concentration. In: Proceedings, 3rd International Congress, Mathematic Modelling of Liver Excretion Processes. Tokyo, Japan: Juntendo University Press; 1990: 312316.
  • 50
    Potter BJ, Sorrentino D, Berk PD. Mechanisms of cellular uptake of free fatty acids. Annu Rev Nutr 1989; 9: 253270.
  • 51
    Sorrentino D, Potter BJ, Berk PD. From albumin to the cytoplasm: the hepatic uptake of organic anions. Prog Liver Dis 1990; IX: 203204.
  • 52
    Stremmel W, Potter BJ, Berk PD. Studies of albumin binding to rat liver plasma membranes: implications for the albumin receptor hypothesis. Biochim Biophys Acta 1983; 756: 2027.
  • 53
    Sorrentino D, Robinson RB, Kiang CL, Berk PD. At physiologic albumin/oleate concentrations oleate uptake by isolated hepatocytes, cardiac myocytes and adipocytes is a saturable function of the unbound oleate concentration. Uptake kinetics are consistent with the conventional theory. J Clin Invest 1989; 84: 13251333.
  • 54
    Sorrrentino D, Zifroni A, Van Ness K, Berk PD. Unbound ligand drives hepatocyte taurocholate and BSP uptake at physiological albumin concentration. Am J Physiol 1994; 266: G425G432.
  • 55
    Sorrentino D, Van Ness K, Berk PD. Oleate uptake kinetics in the perfused rat liver are consistent with pseudofacilitation by albumin. J Hepatol 1994; 21: 551559.
  • 56
    Sorrentino D, Berk PD. Free fatty acids, albumin and the sinusoidal plasma membrane: concepts, trends and controversies. In: Tavoloni N, Berk PD, Eds. Hepatic Transport and Bile Secretion. New York, NY: Raven Press; 1993: 197210.
  • 57
    Potter BJ, Berk PD. Liver plasma membrane fatty acid binding protein. In: Tavoloni N, Berk PD, Eds. Hepatic Transport and Bile Secretion. New York, NY: Raven Press; 1993: 253267.
  • 58
    Stremmel W, Berk PD. Hepatocellular influx of 14C-oleate reflects membrane transport rather than intra-cellular metabolism or binding. Proc Natl Acad Sci U S A 1986; 83: 30863090.
  • 59
    Stremmel W, Strohmeyer G, Berk PD. Hepatocellular uptake of oleate is energy dependent, sodium linked, and inhibited by an antibody to a hepatocyte plasma membrane fatty acid binding protein. Proc Natl Acad Sci U S A 1986; 83: 35843588.
  • 60
    Stump DD, Nunes RM, Sorrentino D, Berk PD. Characteristics of oleate binding to liver plasma membrane and its uptake by isolated hepatocytes. J Hepatol 1992; 16: 304315.
  • 61
    Stremmel W, Kochwa S, Berk PD. Studies of oleate binding to rat liver plasma membranes. Biochem Biophys Res Commun 1983; 112: 8895.
  • 62
    Schwieterman W, Sorrentino D, Potter BJ, Rand J, Kiang CL, Stump D, et al. Uptake of oleate by isolated rat adipocytes is mediated by a 40 kDa plasma membrane fatty acid binding protein closely related to that in liver and gut. Proc Natl Acad Sci U S A 1988; 85: 359363.
  • 63
    Stump DD, Fan X, Berk PD. Oleic acid uptake and binding by rat adipocytes define dual pathways for cellular fatty acid uptake. J Lipid Res 2001; 42: 509520.
  • 64
    Stremmel W, Lotz G, Strohmeyer G, Berk PD. Identification, isolation and partial characterization of a fatty acid binding protein from rat jejunal microvillous membranes. J Clin Invest 1985; 75: 10681076.
  • 65
    Sorrentino D, Stump D, Potter BJ, Robinson R, White R, Kiang CL, et al. Oleate uptake by cardiac myocytes is carrier mediated and involves a 40 kDa plasma membrane fatty acid binding protein similar to that in liver, adipose tissue and gut. J Clin Invest 1988; 82: 928935.
  • 66
    Berk PD, Stump DD. Mechanisms of cellular uptake of long chain free fatty acids. Mol Cell Biochem 1999; 192: 1731.
  • 67
    Stoll GH, Voges R, Gerok W, Kurz G. Synthesis of a metabolically stable modified long-chain fatty acid salt and its photolabile derivative. J Lipid Res 1991; 32: 843857.
  • 68
    Schmider W, Fahr A, Blum HE, Kurz G. Transport of heptafluorostearate across model membranes. Membrane transport of long-chain fatty acid anions I. J Lipid Res 2000; 41: 775787.
  • 69
    Sorrentino D, Zhou SL, Kokkoutou E, Berk PD. Sex differences in hepatic fatty acid uptake reflect a greater affinity of the membrane transport system in females. Am J Physiol Gastrointest Liver Physiol 1992; 263: G380G385.
  • 70
    Sorrentino D, Zhou SL, Van Ness K, Isola LM, Berk PD. The hepatocellular uptake of free fatty acids is selectively preserved during starvation. Gastroenterology 1994; 107: 14151424.
  • 71
    Sorrentino D, Van Ness K, Simard A, Andreas J, Schwab AJ, Stump D, et al. Oleate uptake by isolated hepatocytes and the perfused rat liver is competitively inhibited by palmitate. Am J Physiol 1996; 270: G385G392.
  • 72
    Kamp F, Hamilton JA. pH gradients across phospholipids membranes caused by fast flip-flop of un-ionized fatty acids. Proc Natl Acad Sci U S A 1992; 89: 1136711370.
  • 73
    Kamp F, Westerhoff HV, Hamilton JA. Movement of fatty acids, fatty acid analogues, and bile acids across a phospholipids bilayer. Biochemistry 1993; 32: 1107411086.
  • 74
    Kamp F, Zakim D, Zhang F, Noy N, Hamilton JA. Fatty acid flip-flop in phospholipid bilayers is extremely fast. Biochemistry 1995; 34: 1192811937.
  • 75
    Daniels C, Noy N, Zakim D. Rates of hydration of fatty acids bound to unilamellar vesicles of phosphatidylcholine or to albumin. Biochemistry 1985; 24: 32863292.
  • 76
    Civelek VN, Hamilton JA, Tornheim K, Kelly KL, Corkey BE. Intracellular pH in adipocytes: effects of free fatty acid diffusion across the plasma membrane, lipolytic agonists, and insulin. Proc Natl Acad Sci U S A 1996; 1013910144.
  • 77
    Luiken JJ, Turcotte LP, Bonen A. Protein-mediated palmitate uptake and expression of fatty acid transport proteins in heart giant vesicles. J Lipid Res 1999; 40: 10071016.
  • 78
    Luiken JJ, Glatz JF, Bonen A. Fatty acid transport proteins facilitate fatty acid uptake in skeletal muscle. Can J Appl Physiol 2000; 25: 333352.
  • 79
    Kampf JP, Kleinfeld AM. Fatty acid transport in adipocytes monitored by imaging intracellular free fatty acid levels. J Biol Chem 2004; 279: 3577535780.
  • 80
    Kleinfeld AM, Kampf JP, Lechene C. Transport of 13C-oleate in adipocytes measured using multi imaging mass spectrometry. J Am Soc Mass Spectrom 2004; 15: 15721580.
  • 81
    Stremmel W, Strohmeyer G, Borchard F, Kochwa S, Berk PD. Isolation and partial characterization of a fatty acid binding protein in rat liver plasma membranes. Proc Nat Acad Sci U S A 1985; 82: 48.
  • 82
    Potter BJ, Stump D, Schwieterman W, Sorrentino D, Jacobs LN, Kiang CL, et al: Isolation and partial characterization of plasma membrane fatty acid binding proteins from myocardium and adipose tissue and their relationship to analogous proteins in liver and gut. Biochem Biophys Res Commun 1987; 148: 13701376.
  • 83
    Zhou SL, Stump D, Sorrentino D, Potter BJ, Berk PD. Adipocyte differentiation of 3T3 L1 cells involves augumented expression of a 43 kDa plasma membrane fatty acid binding protein. J Biol Chem 1992; 267: 1445614461.
  • 84
    Zhou SL, Stump DD, Isola LM, Berk PD. Mitochondrial aspartate aminotransferase expressed on the surface of 3T3 L1 adipocytes mediates saturable fatty acid uptake. Proc Soc Exp Biol Med 1995; 208: 263270.
  • 85
    Abumrad NA, el-Maghrabi MR, Amri EZ, Lopez E, Grimaldi PA. Cloning of a rat adipocyte membrane protein implicated in binding or transport of long-chain fatty acids that is induced during preadipocyte differentiation. Homology with human CD36. J Biol Chem 1993; 268: 1766517668.
  • 86
    Schaffer JE, Lodish HF. Expression cloning and characterization of a novel adipocyte long chain fatty acid transport protein. Cell 1994; 79: 427436.
  • 87
    Hirsch D, Stahl A, Lodish HF. A family of fatty acid transporters conserved from mycobacterium to man. Proc Natl Acad Sci U S A 1998; 95: 86258629.
  • 88
    Stahl A, Gimeno RE, Tartaglia LA, Lodish HF. Fatty acid transport proteins: a current view of a growing family. Trends Endocrinol Metab 2001; 12: 266273.
  • 89
    Trigatti BL, Anderson RG, Gerber GE. Identification of caveolin-1 as a fatty acid binding protein. Biochem Biophys Res Commun 1999; 255: 3439.
  • 90
    Pohl J, Ring A, Stremmel W. Uptake of long-chain fatty acids in HepG2 cells involves caveolae: analysis of a novel pathway. J Lipid Res 2002; 43: 13901399.
  • 91
    Kampf JP, Parmley D, Kleinfeld AM. Free fatty acid transport across adipocytes is mediated by an unknown membrane protein pump. Am J Physiol Endocrinol Metab 2007; 293: E1207E1214.
  • 92
    Berk PD, Wada H, Horio Y, Potter BJ, Sorrentino D, Zhou SL, et al. Plasma membrane fatty acid binding protein and mitochondrial glutamic oxaloacetic transaminase of rat liver are related. Proc Natl Acad Sci U S A 1990; 87: 34843488.
  • 93
    Stump DD, Zhou SL, Berk PD. Comparison of the plasma membrane FABP and mitochondrial isoform of aspartate aminotransferase from rat liver. Am J Physiol 1993; 265: G894G902.
  • 94
    Zhou SL, Stump D, Isola LM, Berk PD. Constitutive expression of a saturable transport system for non-esterified fatty acids in Xenopus laevis oocytes. Biochem J 1994; 297: 315319.
  • 95
    Isola LM, Zhou S-L, Kiang C-L, Stump DD, Bradbury MW, Berk PD. 3T3 fibroblasts transfected with a cDNA for mitochondrial aspartate aminotransferase express plasma membrane fatty acid-binding protein and saturable fatty acid uptake. Proc Natl Acad Sci U S A 1995; 92: 98669870.
  • 96
    Bradbury MW, Berk PD. Cellular uptake of long chain free fatty acids: the structure and function of plasma membrane fatty acid binding protein. Adv Mol Cell Biol 2004; 33: 4781.
  • 97
    Zhou SL, Gordon RE, Bradbury M, Stump D, Kiang CL, Berk PD. Ethanol up regulates fatty acid uptake and plasma membrane expression and export of mitochondrial aspartate aminotransferase in HepG2 cells. HEPATOLOGY 1998; 27: 10641074.
  • 98
    Cechetto JD, Sadacharan SK, Berk PD, Gupta RS. Immunogold localization of mitochondrial aspartate aminotransferase in mitochondria and on cell surface in normal rat tissues. Histol Histopathol 2002; 17: 353364.
  • 99
    Berk PD, Delavega L, Stockert RJ. Mitochondrial aspartate aminotransferase reaches the plasma membrane and is exported from HuH7 cells via the golgi/endoplasmic reticulum [Abstract]. HEPATOLOGY 1998; 28: 400A.
  • 100
    Guarnieri F, Stump DD, Roboz J, Yu Q, Berk PD. Mitochondrial aspartateaminotransferase contains a 500-Angstrom3 hydrophobic groove representing a putative fatty-acid-binding site. HEPATOLOGY 1995; 22: 1269.
  • 101
    Bradbury M, Fan XQ, Stump DD, Odin JA, Guarnieri F, Berk PD. Mapping the fatty acid binding site in hepatic plasma membrane fatty acid binding protein with molecular modeling and mutagenesis [Abstract]. HEPATOLOGY 2001; 34: 256A.
  • 102
    Berk PD, Zhou SL, Kiang CL, Stump D, Bradbury M, Isola LM. Uptake of long chain free fatty acids is selectively up-regulated in adipocytes of Zucker rats with genetic obesity and non-insulin-dependent diabetes mellitus. J Biol Chem 1997; 272: 88308835.
  • 103
    Berk PD, Zhou S, Kiang C, Stump DD, Fan X, Bradbury MW. Selective up-regulation of fatty acid uptake by adipocytes characterizes both genetic and diet-induced obesity in rodents. J Biol Chem 1999; 274: 2862628631.
  • 104
    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: 425432.
  • 105
    Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996; 379: 632635.
  • 106
    Chua SC Jr, Chung WK, Wu-Peng XS, Zhang Y, Liu S-M, Tartaglia L, et al. Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 1996; 271: 994996.
  • 107
    Petrescu O, Cheema AF, Fan X, Bradbury MW, Berk PD. Differences in adipocyte uptake of long chain fatty acids in response to high fat diets in Osborne-Mendel and S5B/Pl rats. Int J Obes (Lond) 2008; 32: 853862.
  • 108
    Petrescu O, Fan X, Gentileschi P, Hossain S, Bradbury M, Gagner M, et al. Long-chain fatty acid uptake is upregulated in omental adipocytes from patients undergoing bariatric surgery for obesity. Int J Obes (Lond) 2005; 29: 196203.
  • 109
    Fan X, Bradbury MW, Berk PD. Leptin and insulin modulate energy efficiency and weight loss through selective regulation of long chain fatty acid uptake by adipocytes. J Nutr 2003; 133: 27072715.
  • 110
    Ibrahimi A, Sfeir Z, Magharaie H, Amri EZ, Grimaldi P, Abumrad NA. Expression of the CD36 homolog (FAT) in fibroblast cells: effects on fatty acid transport. Proc Natl Acad Sci U S A 1996; 93: 26462651.
  • 111
    Bradbury MW, Berk PD. Lipid metabolism in hepatic steatosis. Clin Liver Dis 2004; 8: 639671.
  • 112
    The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity—2001. Washington, DC: U.S. Government Printing Office/U.S. Department of Health and Human Services; 2001.
  • 113
    Yanovski SZ, Yanovski JA. Obesity. N Engl J Med 2002; 346: 591602.
  • 114
    Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA 2002; 288: 17231727.
  • 115
    Ogden CL, Yanovski SZ, Carroll MD, Flegal KM. The epidemiology of obesity. Gastroenterology 2007; 132: 20872102.
  • 116
    State-specific prevalence of obesity among adults–United States, 2005. MMWR Morb Mortal Wkly Rep 2006; 55: 985988.
  • 117
    Wanless IR, Lentz JS. Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors. HEPATOLOGY 1990; 12: 11061110.
  • 118
    Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated amino-transferase levels in the United States. Am J Gastroenterol 2003; 98: 960967.
    Direct Link:
  • 119
    Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology 2003; 124: 7179.
  • 120
    Ruhl CE, Everhart JE. Epidemiology of nonalcoholic fatty liver. Clin Liver Dis 2004; 8: 501519, vii.
  • 121
    Browning JD, Szczepaniak LS, Dobbins R, Nuremberg P, Horton JD, Cohen JC, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. HEPATOLOGY 2004; 40: 13871395.
  • 122
    Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 2006; 40(3 Suppl 1 ): S5S10.
  • 123
    Kopelman PG. Obesity as a medical problem. Nature 2000; 404: 635643.
  • 124
    Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. HEPATOLOGY 2005; 41: 13131321.
  • 125
    Bondini S, Kleiner DE, Goodman ZD, Gramlich T, Younossi ZM. Pathologic assessment of non-alcoholic fatty liver disease. Clin Liver Dis 2007; 11: 1723, vii.
  • 126
    Yeh MM, Brunt EM. Pathology of nonalcoholic fatty liver disease. Am J Clin Pathol 2007; 128: 837847.
  • 127
    Brunt EM. Nonalcoholic steatohepatitis: definition and pathology. Semin Liver Dis 2001; 21: 316.
  • 128
    Brunt EM, Neuschwander-Tetri BA, Oliver D, Wehmeier KR, Bacon BR. Nonalcoholic steatohepatitis: histologic features and clinical correlations with 30 blinded biopsy specimens. Hum Pathol 2004; 35: 10701082.
  • 129
    Brunt EM. Nonalcoholic steatohepatitis: pathologic features and differential diagnosis. Semin Diagn Pathol 2005; 22: 330338.
  • 130
    Thung SN, Gerber M. Alcoholic hepatitis vs nonalcoholic steatohepatitis. In: Thung SN, Gerber MA, Eds. Differential Diagnosis in Pathology: Liver Disorders. New York, NY: Igaku-Shoin; 1995: 2436.
  • 131
    Pinto HC, Baptista A, Camilo ME, Valente A, Saragoca A, de Moura MC. Nonalcoholic steatohepatitis. Clinicopathological comparison with alcoholic hepatitis in ambulatory and hospitalized patients. Dig Dis Sci 1996; 41: 172179.
  • 132
    Gramlich T, Kleiner DE, McCullough AJ, Matteoni CA, Boparai N, Younossi ZM. Pathologic features associated with fibrosis in nonalcoholic fatty liver disease. Hum Pathol 2004; 35: 196199.
  • 133
    Leclercq IA, Horsmans Y. Cell biology of NASH: fibrosis and cell proliferation. In: Farrell GC, George J, Hall P de la M, McCullough AK, Eds. Fatty Liver Disease: NASH and Related Disorders. Oxford, UK: Blackwell; 2005: 143158.
  • 134
    Clark JM, Diehl AM. Nonalcoholic fatty liver disease: an under-recognized cause of cryptogenic cirrhosis. JAMA 2003; 289: 30003004.
  • 135
    Caldwell SH, Crespo DM. The spectrum expanded: cryptogenic cirrhosis and the natural history of non-alcoholic fatty liver disease. J Hepatol 2004; 40: 578584.
  • 136
    Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. HEPATOLOGY 2006; 43(2 Suppl 1 ): S99S112.
  • 137
    Charlton M, Kasparova P, Weston S, Lindor K, Maor-Kendler Y, Wiesner RH, et al. Frequency of nonalcoholic steatohepatitis as a cause of advanced liver disease. Liver Transpl 2001; 7: 608614.
  • 138
    Burke A, Lucey MR. Non-alcoholic fatty liver disease, non-alcoholic steatohepatitis and orthotopic liver transplantation. Am J Transplant 2004; 4: 686693.
  • 139
    Charlton M. Nonalcoholic fatty liver disease: a review of current understanding and future impact. Clin Gastroenterol Hepatol 2004; 2: 10481058.
  • 140
    Goldberg IJ, Ginsberg HN. Ins and outs modulating hepatic triglyceride and development of nonalcoholic fatty liver disease. Gastroenterology 2006; 130: 13431346.
  • 141
    Chirieac DV, Chirieac LR, Corsetti JP, Cianci J, Sparks CE, Sparks JD. Glucose-stimulated insulin secretion suppresses hepatic triglyceride-rich lipoprotein and apoB production. Am J Physiol Endocr Metab 2000; 279: E1003E1011.
  • 142
    Diehl AM. Lessons from animal models of NASH. Hepatol Res 2005; 33: 138144.
  • 143
    Rinella ME, Elias MS, Smolak RR, Fu T, Borensztajn J, Green RM. Mechanisms of hepatic steatosis in mice fed a lipogenic methionine choline-deficient diet. J Lipid Res 2008; 49: 10681076.
  • 144
    Minehira K, Young SG, Villanueva CJ, Yetukuri L, Oresic M, Hellerstein MK,et al. Blocking VLDL secretion causes hepatic steatosis but does not affect peripheral lipid stores or insulin sensitivity in mice. J Lipid Res 2008; 49: 20382044.
  • 145
    Day CP, James OF. Steatohepatitis: a tale of two “hits”? Gastroenterology 1998; 114: 842845.
  • 146
    McCullough AJ. Pathophysiology of nonalcoholic steatohepatitis. J Clin Gastroenterol 2006; 40(3 Suppl 1 ): S17S29.
  • 147
    Merriman RB, Aouizerat BE, Bass NM. Genetic influences in nonalcoholic fatty liver disease. J Clin Gastroenterol 2006; 40(3 Suppl 1 ): S30S33.
  • 148
    Mantena SK, King AL, Andringa KK, Eccleston HB, Bailey SM. Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases. Free Radic Biol Med 2008; 44: 12591272.
  • 149
    Malhi H, Gores G. Molecular mechanisms of lipotoxicity in nonalcoholic fatty liver disease. Semin Liv Dis 2008; 28: 360369.
  • 150
    Jou J, Choi SC, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin Liv Dis 2008; 28: 370379.
  • 151
    Leclercq IA, Farrell GC, Field J, Bell DR, Gonzalez FJ, Robertson GR. CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitis. J Clin Invest 2000; 105: 10671075.
  • 152
    Robertson G, Leclercq I, Farrell GC. Nonalcoholic steatosis and steatohepatitis. II. Cytochrome P-450 enzymes and oxidative stress. Am J Physiol Gastrointest Liver Physiol 2001; 281: G1135G1139.
  • 153
    Sanyal AJ, Campbell-Sargent C, Mirshahi F, Rizzo WB, Contos MJ, Sterling RK, et al. Nonalcoholic steatohepatitis: association of insulin resistance and mitochondrial abnormalities. Gastroenterology 2001; 120: 11831192.
  • 154
    De Minicis S, Brenner DA. Oxidative stress in alcoholic liver disease: role of NADPH oxidase complex. J Gastroenterol Hepatol 2008; 23(Suppl 1): S98S103.
  • 155
    Verna EC, Berk PD. Role of fatty acids in the pathogenesis of obesity and fatty liver: Impact of bariatric surgery. Semin Liver Dis 2008; 28: 407426.
  • 156
    Grundy SM, Brewer HB Jr, Cleeman JI, Smith SC Jr, Lenfant C. Definition of metabolic syndrome: report of the National Heart, Lung, and Blood Institute/American Heart Association conference on scientific issues related to definition. Arterioscler Thromb Vasc Biol 2004; 24: e13e18.
  • 157
    Reaven G. Metabolic syndrome: pathophysiology and implications for management of cardiovascular disease. Circulation 2002; 106: 286288.
  • 158
    Haynes P, Liangpunsakul S, Chalasani N. Nonalcoholic fatty liver disease in individuals with severe obesity. Clin Liver Dis 2004; 8: 535547, viii.
  • 159
    Choudhury J, Sanyal AJ. Insulin resistance and the pathogenesis of nonalcoholic fatty liver disease. Clin Liver Dis 2004; 8: 575594, ix.
  • 160
    Marceau P, Biron S, Hould FS, Marceau S, Simard S, Thung SN, et al. Liver pathology and the metabolic syndrome X in severe obesity. J Clin Endocrinol Metab 1999; 84: 15131517.
  • 161
    Kahn R, Buse J, Ferrannini E, Stern M. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2005; 28: 22892304.
  • 162
    Reaven GM. The individual components of the metabolic syndrome: is there a raison d'etre? J Am Coll Nutr 2007; 26: 191195.
  • 163
    Pagano G, Pacini G, Musso G, Gambino R, Mecca F, Depetris N, et al. Nonalcoholic steatohepatitis, insulin resistance, and metabolic syndrome: further evidence for an etiologic association. HEPATOLOGY 2002; 35: 367372.
  • 164
    Wisse BE. The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 2004; 15: 27922800.
  • 165
    Kerner A, Avizohar O, Sella R, Bartha P, Zinder O, Markiewicz W, et al. Association between elevated liver enzymes and C-reactive protein: possible hepatic contribution to systemic inflammation in the metabolic syndrome. Arterioscler Thromb Vasc Biol 2005; 25: 193197.
  • 166
    Ferroni P, Basili S, Falco A, Davi G. Inflammation, insulin resistance, and obesity. Curr Atheroscler Rep 2004; 6: 424431.
  • 167
    McGarry JD, Dobbins RL. Fatty acids, lipotoxicity and insulin secretion. Diabetologia 1999; 42: 128138.
  • 168
    Unger RH, Orci L. Lipotoxic diseases of nonadipose tissues in obesity. Int J Obes Relat Metab Disord 2000; 24(Suppl 4): S28S32.
  • 169
    Unger RH. Lipotoxic diseases. Annu Rev Med 2002; 53: 319336.
  • 170
    Unger RH. Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome. Endocrinology 2003; 144: 51595165.
  • 171
    Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol 2003; 14: 281287.
  • 172
    Abdul-Ghani MA, Muller FL, Liu Y, Chavez AO, Balas B, Zuo P, et al. Deleterious action of FA metabolites on ATP synthesis: The link between lipotoxicity, mitochondrial dysfunction and insulin resistance. Am J Physiol Endocrinol Metab 2008; 295: E678E685.
  • 173
    Duncan JG. Lipotoxicity: what is the fate of fatty acids? J Lipid Res 2008; 49: 13751376.
  • 174
    Berk PD, Zhou SL, Bradbury MW. Increased hepatocellular uptake of long chain fatty acids occurs by different mechanisms in fatty livers due to obesity or excess ethanol use, contributing to development of steatohepatitis in both settings. Trans Am Clin Climatol Assoc 2005; 116: 335345.
  • 175
    Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN. Bilirubin is an antioxidant of possible physiological importance. Science 1987; 235: 10431046.
  • 176
    Rigato I, Ostrow JD, Tiribelli C. Bilirubin and the risk of common non-hepatic diseases. Trends Mol Med 2005; 11: 277283.
  • 177
    Shekeeb Shahab M, Kumar P, Sharma N, Narang A, Prasad R. Evaluation of oxidant and antioxidant status in term neonates: a plausible protective role of bilirubin. Mol Cell Biochem 2008; doi: 10.1007/s11010-008-9807-4.
  • 178
    Heisenberg W. Über den anschaulichen Inhalt der quantentheoretischen Kinematik und Mechanik. Z Phys 1927; 43: 172198.
  • 179
    Zhou S, Twaddell WS, Carras E, Lefkowitch J, Berk PD. Dose-dependent effects of ethanol on adipocyte, hepatocyte and cardiac myocyte fatty acid uptake and triglyceride accumulation in C57BL/6J mice [Abstract]. HEPATOLOGY 2007; 46(4 Suppl 1 ): 325A.
  • 180
    Zhou S, Ge F, Berk PD. Comparison of plasma insulin and leptin concentrations with long chain fatty acid uptake in hepatocytes and adipocytes from mice with hepatic steatosis clarifies the hormonal regulation of fatty acid disposition [Abstract]. Gastroenterology 2008; 134(4 Suppl 1 ): A-778.
  • 181
    Ge F, Arai K, Zhou S, Homma S, Berk PD. Histologic and echocardiographic evidence of lipid-associated cardiomyopathy in multiple mouse obesity models [Abstract]. Obesity 2008; 16(9 Progr Abstr Suppl) S106S107.
  • 182
    Unger RH. The physiology of liporegulation. Annu Rev Physiol 2003; 65: 333347.
  • 183
    Wong C, Marwick TH. Obesity cardiomyopathy: pathogenesis and pathophysiology. Nat Clin Pract Cardiovasc Med 2007; 4: 436443.
  • 184
    Wong C, Marwick T. Obesity cardiomyopathy: diagnosis and therapeutic implications. Nat Clin Practice 2007; 4: 480490.
  • 185
    McGavock JM, Victor RG, Unger RH, Szczepaniak LS. Adiposity of the heart, revisited. Ann Intern Med 2006; 144: 517524.
  • 186
    Belke DD, Larsen TS, Gibbs EM, Severson DL. Altered metabolism causes cardiac dysfunction in perfused hearts from diabetic (db/db) mice. Am J Physiol Endocrinol Metab 2000; 279: E1104E1113.
  • 187
    Chiu H-C, Kovacs A, Ford DA, Hsu F-F, Garcia R, Herrero P, et al. A novel mouse model of lipotoxic cardiomyopathy. J Clin Invest 2001; 107: 813822.
  • 188
    Yang J, Sambandam N, Han X, Gross RW, Courtois M, Kovacs A, et al. CD36 deficiency rescues lipotoxic cardiomyopathy. Circ Res 2007; 100: 12081217.
  • 189
    Lee Y, Naseem RH, Park BH, Garry DJ, Richardson JA, Schaffer JE, et al. Alpha-lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice. Biochem Biophys Res Commun 2006; 344: 446452.
  • 190
    Chiu HC, Kovacs A, Blanton RM, Han X, Courtois M, Weinheimer CJ, et al. Transgenic expression of fatty acid transport protein 1 in the heart causes lipotoxic cardiomyopathy. Circ Res 2005; 96: 225233.