• 1
    Petersen KF, Oral EA, Dufour S, Befroy D, Ariyan C, Yu C, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. J Clin Invest 2002; 109: 1345-1350.
  • 2
    Seppala-Lindroos A, Vehkavaara S, Hakkinen AM, Goto T, Westerbacka J, Sovijarvi A, et al. Fat accumulation in the liver is associated with defects in insulin suppression of glucose production and serum free fatty acids independent of obesity in normal men. J Clin Endocrinol Metab 2002; 87: 3023-3028.
  • 3
    Petersen KF, Dufour S, Befroy D, Lehrke M, Hendler RE, Shulman GI. Reversal of nonalcoholic hepatic steatosis, hepatic insulin resistance, and hyperglycemia by moderate weight reduction in patients with type 2 diabetes. Diabetes 2005; 54: 603-608.
  • 4
    Ito Y, Azrolan N, O'Connell A, Walsh A, Breslow JL. Hypertriglyceridemia as a result of human apo CIII gene expression in transgenic mice. Science 1990; 249: 790-793.
  • 5
    Pollin TI, Damcott CM, Shen H, Ott SH, Shelton J, Horenstein RB, et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science 2008; 322: 1702-1705.
  • 6
    Aalto-Setala K, Fisher EA, Chen X, Chajek-Shaul T, Hayek T, Zechner R, et al. Mechanism of hypertriglyceridemia in human apolipoprotein (apo) CIII transgenic mice. Diminished very low density lipoprotein fractional catabolic rate associated with increased apo CIII and reduced apo E on the particles. J Clin Invest 1992; 90: 1889-1900.
  • 7
    Sundaram M, Zhong S, Bou Khalil M, Links PH, Zhao Y, Iqbal J, et al. Expression of apolipoprotein C-III in McA-RH7777 cells enhances VLDL assembly and secretion under lipid-rich conditions. J Lipid Res 2010; 51: 150-161.
  • 8
    Cohn JS, Patterson BW, Uffelman KD, Davignon J, Steiner G. Rate of production of plasma and very-low-density lipoprotein (VLDL) apolipoprotein C-III is strongly related to the concentration and level of production of VLDL triglyceride in male subjects with different body weights and levels of insulin sensitivity. J Clin Endocrinol Metab 2004; 89: 3949-3955.
  • 9
    Petersen KF, Dufour S, Hariri A, Nelson-Williams C, Foo JN, Zhang XM, et al. Apolipoprotein C3 gene variants in nonalcoholic fatty liver disease. N Engl J Med 2010; 362: 1082-1089.
  • 10
    Kawakami A, Aikawa M, Alcaide P, Luscinskas FW, Libby P, Sacks FM. Apolipoprotein CIII induces expression of vascular cell adhesion molecule-1 in vascular endothelial cells and increases adhesion of monocytic cells. Circulation 2006; 114: 681-687.
  • 11
    Abe Y, Kawakami A, Osaka M, Uematsu S, Akira S, Shimokado K, et al. Apolipoprotein CIII induces monocyte chemoattractant protein-1 and interleukin 6 expression via Toll-like receptor 2 pathway in mouse adipocytes. Arterioscler Thromb Vasc Biol 2010; 30: 2242-2248.
  • 12
    Pollex RL, Ban MR, Young TK, Bjerregaard P, Anand SS, Yusuf S, et al. Association between the -455T>C promoter polymorphism of the APOC3 gene and the metabolic syndrome in a multi-ethnic sample. BMC Med Genet 2007; 8: 80.
  • 13
    Waterworth DM, Ribalta J, Nicaud V, Dallongeville J, Humphries SE, Talmud P. ApoCIII gene variants modulate postprandial response to both glucose and fat tolerance tests. Circulation 1999; 99: 1872-1877.
  • 14
    Lee HY, Park JH, Seok SH, Baek MW, Kim DJ, Lee KE, et al. Human originated bacteria, Lactobacillus rhamnosus PL60, produce conjugated linoleic acid and show anti-obesity effects in diet-induced obese mice. Biochim Biophys Acta 2006; 1761: 736-744.
  • 15
    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: 1313-1321.
  • 16
    Lee HY, Choi CS, Birkenfeld AL, Alves TC, Jornayvaz FR, Jurczak MJ, et al. Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance. Cell Metab 2010; 12: 668-674.
  • 17
    Samuel VT, Choi CS, Phillips TG, Romanelli AJ, Geisler JG, Bhanot S, et al. Targeting foxo1 in mice using antisense oligonucleotide improves hepatic and peripheral insulin action. Diabetes 2006; 55: 2042-2050.
  • 18
    Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1959; 37: 911-917.
  • 19
    Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, et al. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem 2002; 277: 50230-50236.
  • 20
    Samuel VT, Liu ZX, Qu X, Elder BD, Bilz S, Befroy D, et al. Mechanism of hepatic insulin resistance in non-alcoholic fatty liver disease. J Biol Chem 2004; 279: 32345-32353.
  • 21
    Choi CS, Fillmore JJ, Kim JK, Liu ZX, Kim S, Collier EF, et al. Overexpression of uncoupling protein 3 in skeletal muscle protects against fat-induced insulin resistance. J Clin Invest 2007; 117: 1995-2003.
  • 22
    Bharadwaj KG, Hiyama Y, Hu Y, Huggins LA, Ramakrishnan R, Abumrad NA, et al. Chylomicron- and VLDL-derived lipids enter the heart through different pathways: in vivo evidence for receptor- and non-receptor-mediated fatty acid uptake. J Biol Chem 2010; 285: 37976-37986.
  • 23
    Ginsberg HN, Brown WV. Apolipoprotein CIII: 42 years old and even more interesting. Arterioscler Thromb Vasc Biol 2011; 31: 471-473.
  • 24
    Salhanick AI, Schwartz SI, Amatruda JM. Insulin inhibits apolipoprotein B secretion in isolated human hepatocytes. Metabolism 1991; 40: 275-279.
  • 25
    Sparks JD, Sparks CE. Insulin regulation of triacylglycerol-rich lipoprotein synthesis and secretion. Biochim Biophys Acta 1994; 1215: 9-32.
  • 26
    Lewis GF, Steiner G. Acute effects of insulin in the control of VLDL production in humans. Implications for the insulin-resistant state. Diabetes Care 1996; 19: 390-393.
  • 27
    Sorensen LP, Andersen IR, Sondergaard E, Gormsen LC, Schmitz O, Christiansen JS, et al. Basal and insulin mediated VLDL-triglyceride kinetics in type 2 diabetic men. Diabetes 2011; 60: 88-96.
  • 28
    Reaven GM, Mondon CE, Chen YD, Breslow JL. Hypertriglyceridemic mice transgenic for the human apolipoprotein C-III gene are neither insulin resistant nor hyperinsulinemic. J Lipid Res 1994; 35: 820-824.
  • 29
    Kawakami A, Osaka M, Aikawa M, Uematsu S, Akira S, Libby P, et al. Toll-like receptor 2 mediates apolipoprotein CIII-induced monocyte activation. Circ Res 2008; 103: 1402-1409.
  • 30
    Samuel VT, Liu ZX, Wang A, Beddow SA, Geisler JG, Kahn M, et al. Inhibition of protein kinase Cepsilon prevents hepatic insulin resistance in nonalcoholic fatty liver disease. J Clin Invest 2007; 117: 739-745.
  • 31
    Romeo S, Kozlitina J, Xing C, Pertsemlidis A, Cox D, Pennacchio LA, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet 2008; 40: 1461-1465.
  • 32
    Rull A, Escola-Gil JC, Julve J, Rotllan N, Calpe-Berdiel L, Coll B, et al. Deficiency in monocyte chemoattractant protein-1 modifies lipid and glucose metabolism. Exp Mol Pathol 2007; 83: 361-366.
  • 33
    Rull A, Rodriguez F, Aragones G, Marsillach J, Beltran R, Alonso-Villaverde C, et al. Hepatic monocyte chemoattractant protein-1 is upregulated by dietary cholesterol and contributes to liver steatosis. Cytokine 2009; 48: 273-279.
  • 34
    Lohmann C, Schafer N, von Lukowicz T, Sokrates Stein MA, Boren J, Rutti S, et al. Atherosclerotic mice exhibit systemic inflammation in periadventitial and visceral adipose tissue, liver, and pancreatic islets. Atherosclerosis 2009; 207: 360-367.
  • 35
    de Silva HV, Lauer SJ, Wang J, Simonet WS, Weisgraber KH, Mahley RW, et al. Overexpression of human apolipoprotein C-III in transgenic mice results in an accumulation of apolipoprotein B48 remnants that is corrected by excess apolipoprotein E. J Biol Chem 1994; 269: 2324-2335.
  • 36
    Ebara T, Ramakrishnan R, Steiner G, Shachter NS. Chylomicronemia due to apolipoprotein CIII overexpression in apolipoprotein E-null mice. Apolipoprotein CIII-induced hypertriglyceridemia is not mediated by effects on apolipoprotein E. J Clin Invest 1997; 99: 2672-2681.
  • 37
    Conde-Knape K, Okada K, Ramakrishnan R, Shachter NS. Overexpression of apoC-III produces lesser hypertriglyceridemia in apoB-48-only gene-targeted mice than in apoB-100-only mice. J Lipid Res 2004; 45: 2235-2244.