HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) An addition or correction has been published Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taghibiglou, C. Articles by Adeli, K. Search for Related Content PubMed PubMed Citation Articles by Taghibiglou, C. Articles by Adeli, K. Social Bookmarking                      What's this?

J Biol Chem, Vol. 275, Issue 12, 8416-8425, March 24, 2000

Mechanisms of Hepatic Very Low Density Lipoprotein Overproduction in Insulin Resistance
EVIDENCE FOR ENHANCED LIPOPROTEIN ASSEMBLY, REDUCED INTRACELLULAR ApoB DEGRADATION, AND INCREASED MICROSOMAL TRIGLYCERIDE TRANSFER PROTEIN IN A FRUCTOSE-FED HAMSTER MODEL^*

Changiz Taghibiglou, André Carpentier^§, Stephen C. Van Iderstine, Biao Chen, Debbie Rudy, Andrea Aiton, Gary F. Lewis^§, and Khosrow Adeli^¶

From the  Department of Laboratory Medicine and Pathobiology, Hospital for Sick Children, University of Toronto, and the ^§ Department of Medicine, Division of Endocrinology and Metabolism, The Toronto Hospital, University of Toronto, Toronto, Ontario M5G 1X8, Canada

A novel animal model of insulin resistance, the fructose-fed Syrian golden hamster, was employed to investigate the mechanisms mediating the overproduction of very low density lipoprotein (VLDL) in the insulin resistant state. Fructose feeding for a 2-week period induced significant hypertriglyceridemia and hyperinsulinemia, and the development of whole body insulin resistance was documented using the euglycemic-hyperinsulinemic clamp technique. In vivo Triton WR-1339 studies showed evidence of VLDL-apoB overproduction in the fructose-fed hamster. Fructose feeding induced a significant increase in cellular synthesis and secretion of total triglyceride (TG) as well as VLDL-TG by primary hamster hepatocytes. Increased TG secretion was accompanied by a 4.6-fold increase in VLDL-apoB secretion. Enhanced stability of nascent apoB in fructose-fed hepatocytes was evident in intact cells as well as in a permeabilized cell system. Analysis of newly formed lipoprotein particles in hepatic microsomes revealed significant differences in the pattern and density of lipoproteins, with hepatocytes derived from fructose-fed hamsters having higher levels of luminal lipoproteins at a density of VLDL versus controls. Immunoblot analysis of the intracellular mass of microsomal triglyceride transfer protein, a key enzyme involved in VLDL assembly, showed a striking 2.1-fold elevation in hepatocytes derived from fructose-fed versus control hamsters. Direct incubation of hamster hepatocytes with various concentrations of fructose failed to show any direct stimulation of its intracellular stability or extracellular secretion, further supporting the notion that the apoB overproduction in the fructose-fed hamster may be related to the fructose-induced insulin resistance in this animal model. In summary, hepatic VLDL-apoB overproduction in fructose-fed hamsters appears to result from increased intracellular stability of nascent apoB and an enhanced expression of MTP, which act to facilitate the assembly and secretion of apoB-containing lipoprotein particles.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. Tsai, R. Zhang, W. Qiu, Q. Su, M. Naples, and K. Adeli Inflammatory NF-{kappa}B activation promotes hepatic apolipoprotein B100 secretion: evidence for a link between hepatic inflammation and lipoprotein production Am J Physiol Gastrointest Liver Physiol, June 1, 2009; 296(6): G1287 - G1298. [Abstract] [Full Text] [PDF]

				S. J. Hernandez Vallejo, M. Alqub, S. Luquet, C. Cruciani-Guglielmacci, P. Delerive, J.-M. Lobaccaro, A.-D. Kalopissis, J. Chambaz, M. Rousset, and J.-M. Lacorte Short-term adaptation of postprandial lipoprotein secretion and intestinal gene expression to a high-fat diet Am J Physiol Gastrointest Liver Physiol, April 1, 2009; 296(4): G782 - G792. [Abstract] [Full Text] [PDF]

				H. N. Ginsberg and E. A. Fisher The ever-expanding role of degradation in the regulation of apolipoprotein B metabolism J. Lipid Res., April 1, 2009; 50(Supplement): S162 - S166. [Abstract] [Full Text] [PDF]

				W.-S. Au, L. Lu, C.-M. Yeung, C.-C. Liu, O. G Wong, L. Lai, H.-f. Kung, and M. C Lin Hepatocyte nuclear factor 1 binding element within the promoter of microsomal triglyceride transfer protein (MTTP) gene is crucial for MTTP basal expression and insulin responsiveness J. Mol. Endocrinol., October 1, 2008; 41(4): 229 - 238. [Abstract] [Full Text] [PDF]

				Z. Chen, E. P. Newberry, J. Y. Norris, Y. Xie, J. Luo, S. M. Kennedy, and N. O. Davidson ApoB100 is required for increased VLDL-triglyceride secretion by microsomal triglyceride transfer protein in ob/ob mice J. Lipid Res., September 1, 2008; 49(9): 2013 - 2022. [Abstract] [Full Text] [PDF]

				H. Duez, B. Lamarche, K. D. Uffelman, R. Valero, L. Szeto, S. Lemieux, J. S. Cohn, and G. F. Lewis Dissociation between the Insulin-Sensitizing Effect of Rosiglitazone and Its Effect on Hepatic and Intestinal Lipoprotein Production J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1722 - 1729. [Abstract] [Full Text] [PDF]

				B. Qin, R. A. Anderson, and K. Adeli Tumor necrosis factor-{alpha} directly stimulates the overproduction of hepatic apolipoprotein B100-containing VLDL via impairment of hepatic insulin signaling Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1120 - G1129. [Abstract] [Full Text] [PDF]

				Y.-L. Zhang, A. Hernandez-Ono, P. Siri, S. Weisberg, D. Conlon, M. J. Graham, R. M. Crooke, L.-S. Huang, and H. N. Ginsberg Aberrant Hepatic Expression of PPAR{gamma}2 Stimulates Hepatic Lipogenesis in a Mouse Model of Obesity, Insulin Resistance, Dyslipidemia, and Hepatic Steatosis J. Biol. Chem., December 8, 2006; 281(49): 37603 - 37615. [Abstract] [Full Text] [PDF]

				L. C. Gormsen, M. D. Jensen, O. Schmitz, N. Moller, J. S. Christiansen, and S. Nielsen Energy expenditure, insulin, and VLDL-triglyceride production in humans J. Lipid Res., October 1, 2006; 47(10): 2325 - 2332. [Abstract] [Full Text] [PDF]

				D. V. Chirieac, N. O. Davidson, C. E. Sparks, and J. D. Sparks PI3-kinase activity modulates apo B available for hepatic VLDL production in apobec-1-/- mice Am J Physiol Gastrointest Liver Physiol, September 1, 2006; 291(3): G382 - G388. [Abstract] [Full Text] [PDF]

				L. M. Federico, M. Naples, D. Taylor, and K. Adeli Intestinal Insulin Resistance and Aberrant Production of Apolipoprotein B48 Lipoproteins in an Animal Model of Insulin Resistance and Metabolic Dyslipidemia: Evidence for Activation of Protein Tyrosine Phosphatase-1B, Extracellular Signal-Related Kinase, and Sterol Regulatory Element-Binding Protein-1c in the Fructose-Fed Hamster Intestine. Diabetes, May 1, 2006; 55(5): 1316 - 1326. [Abstract] [Full Text] [PDF]

				S. Bilz, V. Samuel, K. Morino, D. Savage, C. S. Choi, and G. I. Shulman Activation of the farnesoid X receptor improves lipid metabolism in combined hyperlipidemic hamsters Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E716 - E722. [Abstract] [Full Text] [PDF]

				N. S. Raikwar, W. K. Cho, R. F. Bowen, and M. A. Deeg Glycosylphosphatidylinositol-specific phospholipase D influences triglyceride-rich lipoprotein metabolism Am J Physiol Endocrinol Metab, March 1, 2006; 290(3): E463 - E470. [Abstract] [Full Text] [PDF]

				M. Myerson, C. Ngai, J. Jones, S. Holleran, R. Ramakrishnan, L. Berglund, and H. N. Ginsberg Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia J. Lipid Res., December 1, 2005; 46(12): 2735 - 2744. [Abstract] [Full Text] [PDF]

				M. Adiels, J. Boren, M. J. Caslake, P. Stewart, A. Soro, J. Westerbacka, B. Wennberg, S.-O. Olofsson, C. Packard, and M.-R. Taskinen Overproduction of VLDL1 Driven by Hyperglycemia Is a Dominant Feature of Diabetic Dyslipidemia Arterioscler. Thromb. Vasc. Biol., August 1, 2005; 25(8): 1697 - 1703. [Abstract] [Full Text] [PDF]

				E. M. Allister, N. M. Borradaile, J. Y. Edwards, and M. W. Huff Inhibition of Microsomal Triglyceride Transfer Protein Expression and Apolipoprotein B100 Secretion by the Citrus Flavonoid Naringenin and by Insulin Involves Activation of the Mitogen-Activated Protein Kinase Pathway in Hepatocytes Diabetes, June 1, 2005; 54(6): 1676 - 1683. [Abstract] [Full Text] [PDF]

				Y.-H. Yu and H. N. Ginsberg Adipocyte Signaling and Lipid Homeostasis: Sequelae of Insulin-Resistant Adipose Tissue Circ. Res., May 27, 2005; 96(10): 1042 - 1052. [Abstract] [Full Text] [PDF]

				J.-P. F. Morand, J. Macri, and K. Adeli Proteomic Profiling of Hepatic Endoplasmic Reticulum-associated Proteins in an Animal Model of Insulin Resistance and Metabolic Dyslipidemia J. Biol. Chem., May 6, 2005; 280(18): 17626 - 17633. [Abstract] [Full Text] [PDF]

				L. Cordain, S B. Eaton, A. Sebastian, N. Mann, S. Lindeberg, B. A Watkins, J. H O'Keefe, and J. Brand-Miller Origins and evolution of the Western diet: health implications for the 21st century Am. J. Clinical Nutrition, February 1, 2005; 81(2): 341 - 354. [Abstract] [Full Text] [PDF]

				G. F. Lewis, K. Uffelman, M. Naples, L. Szeto, M. Haidari, and K. Adeli Intestinal Lipoprotein Overproduction, a Newly Recognized Component of Insulin Resistance, Is Ameliorated by the Insulin Sensitizer Rosiglitazone: Studies in the Fructose-Fed Syrian Golden Hamster Endocrinology, January 1, 2005; 146(1): 247 - 255. [Abstract] [Full Text] [PDF]

				W. Qiu, R. K. Avramoglu, N. Dube, T. M. Chong, M. Naples, C. Au, K. G. Sidiropoulos, G. F. Lewis, J. S. Cohn, M. L. Tremblay, et al. Hepatic PTP-1B Expression Regulates the Assembly and Secretion of Apolipoprotein B-Containing Lipoproteins: Evidence From Protein Tyrosine Phosphatase-1B Overexpression, Knockout, and RNAi Studies Diabetes, December 1, 2004; 53(12): 3057 - 3066. [Abstract] [Full Text] [PDF]

				G. F. Lewis, S. Murdoch, K. Uffelman, M. Naples, L. Szeto, A. Albers, K. Adeli, and J. D. Brunzell Hepatic Lipase mRNA, Protein, and Plasma Enzyme Activity Is Increased in the Insulin-Resistant, Fructose-Fed Syrian Golden Hamster and Is Partially Normalized by the Insulin Sensitizer Rosiglitazone Diabetes, November 1, 2004; 53(11): 2893 - 2900. [Abstract] [Full Text] [PDF]

				G. F. Lewis, M. Naples, K. Uffelman, N. Leung, L. Szeto, and K. Adeli Intestinal Lipoprotein Production Is Stimulated by an Acute Elevation of Plasma Free Fatty Acids in the Fasting State: Studies in Insulin-Resistant and Insulin-Sensitized Syrian Golden Hamsters Endocrinology, November 1, 2004; 145(11): 5006 - 5012. [Abstract] [Full Text] [PDF]

				Y.-L. Zhang, A. Hernandez-Ono, C. Ko, K. Yasunaga, L.-S. Huang, and H. N. Ginsberg Regulation of Hepatic Apolipoprotein B-lipoprotein Assembly and Secretion by the Availability of Fatty Acids: I. DIFFERENTIAL RESPONSE TO THE DELIVERY OF FATTY ACIDS VIA ALBUMIN OR REMNANT-LIKE EMULSION PARTICLES J. Biol. Chem., April 30, 2004; 279(18): 19362 - 19374. [Abstract] [Full Text] [PDF]

				M. Zoltowska, E. Ziv, E. Delvin, M. Lambert, E. Seidman, and E. Levy Both Insulin Resistance and Diabetes in Psammomys obesus Upregulate the Hepatic Machinery Involved in Intracellular VLDL Assembly Arterioscler. Thromb. Vasc. Biol., January 1, 2004; 24(1): 118 - 123. [Abstract] [Full Text] [PDF]

				C. Ameen and J. Oscarsson Sex Difference in Hepatic Microsomal Triglyceride Transfer Protein Expression Is Determined by the Growth Hormone Secretory Pattern in the Rat Endocrinology, September 1, 2003; 144(9): 3914 - 3921. [Abstract] [Full Text] [PDF]

				K. Ouguerram, T. Magot, Y. Zair, J. S. Marchini, B. Charbonnel, H. Laouenan, and M. Krempf Effect of Atorvastatin on Apolipoprotein B100 Containing Lipoprotein Metabolism in Type-2 Diabetes J. Pharmacol. Exp. Ther., July 1, 2003; 306(1): 332 - 337. [Abstract] [Full Text] [PDF]

				W.-S. Au, H.-f. Kung, and M. C. Lin Regulation of Microsomal Triglyceride Transfer Protein Gene by Insulin in HepG2 Cells: Roles of MAPKerk and MAPKp38 Diabetes, May 1, 2003; 52(5): 1073 - 1080. [Abstract] [Full Text] [PDF]

				S. S Elliott, N. L Keim, J. S Stern, K. Teff, and P. J Havel Fructose, weight gain, and the insulin resistance syndrome Am. J. Clinical Nutrition, November 1, 2002; 76(5): 911 - 922. [Abstract] [Full Text] [PDF]

				F. Pont, L. Duvillard, E. Florentin, P. Gambert, and B. Verges Early Kinetic Abnormalities of ApoB-Containing Lipoproteins in Insulin-Resistant Women With Abdominal Obesity Arterioscler. Thromb. Vasc. Biol., October 1, 2002; 22(10): 1726 - 1732. [Abstract] [Full Text] [PDF]

				M. Haidari, N. Leung, F. Mahbub, K. D. Uffelman, R. Kohen-Avramoglu, G. F. Lewis, and K. Adeli Fasting and Postprandial Overproduction of Intestinally Derived Lipoproteins in an Animal Model of Insulin Resistance. EVIDENCE THAT CHRONIC FRUCTOSE FEEDING IN THE HAMSTER IS ACCOMPANIED BY ENHANCED INTESTINAL DE NOVO LIPOGENESIS AND ApoB48-CONTAINING LIPOPROTEIN OVERPRODUCTION J. Biol. Chem., August 23, 2002; 277(35): 31646 - 31655. [Abstract] [Full Text] [PDF]

				A. Carpentier, C. Taghibiglou, N. Leung, L. Szeto, S. C. Van Iderstine, K. D. Uffelman, R. Buckingham, K. Adeli, and G. F. Lewis Ameliorated Hepatic Insulin Resistance Is Associated with Normalization of Microsomal Triglyceride Transfer Protein Expression and Reduction in Very Low Density Lipoprotein Assembly and Secretion in the Fructose-fed Hamster J. Biol. Chem., August 2, 2002; 277(32): 28795 - 28802. [Abstract] [Full Text] [PDF]

				N. Roglans, E. Sanguino, C. Peris, M. Alegret, M. Vazquez, T. Adzet, C. Diaz, G. Hernandez, J. C. Laguna, and R. M. Sanchez Atorvastatin Treatment Induced Peroxisome Proliferator-Activated Receptor alpha Expression and Decreased Plasma Nonesterified Fatty Acids and Liver Triglyceride in Fructose-Fed Rats J. Pharmacol. Exp. Ther., July 1, 2002; 302(1): 232 - 239. [Abstract] [Full Text] [PDF]

				A. Carpentier, B. W. Patterson, N. Leung, and G. F. Lewis Sensitivity to Acute Insulin-Mediated Suppression of Plasma Free Fatty Acids Is Not a Determinant of Fasting VLDL Triglyceride Secretion in Healthy Humans Diabetes, June 1, 2002; 51(6): 1867 - 1875. [Abstract] [Full Text] [PDF]

				E. A. Fisher and H. N. Ginsberg Complexity in the Secretory Pathway: The Assembly and Secretion of Apolipoprotein B-containing Lipoproteins J. Biol. Chem., May 10, 2002; 277(20): 17377 - 17380. [Full Text] [PDF]

				G. F. Lewis, A. Carpentier, K. Adeli, and A. Giacca Disordered Fat Storage and Mobilization in the Pathogenesis of Insulin Resistance and Type 2 Diabetes Endocr. Rev., April 1, 2002; 23(2): 201 - 229. [Abstract] [Full Text] [PDF]

				E. D. Bartels, M. Lauritsen, and L. B. Nielsen Hepatic Expression of Microsomal Triglyceride Transfer Protein and In Vivo Secretion of Triglyceride-Rich Lipoproteins Are Increased in Obese Diabetic Mice Diabetes, April 1, 2002; 51(4): 1233 - 1239. [Abstract] [Full Text] [PDF]

				C. Taghibiglou, F. Rashid-Kolvear, S. C. Van Iderstine, H. Le-Tien, I. G. Fantus, G. F. Lewis, and K. Adeli Hepatic Very Low Density Lipoprotein-ApoB Overproduction Is Associated with Attenuated Hepatic Insulin Signaling and Overexpression of Protein-tyrosine Phosphatase 1B in a Fructose-fed Hamster Model of Insulin Resistance J. Biol. Chem., January 4, 2002; 277(1): 793 - 803. [Abstract] [Full Text]

				P. Siri, N. Candela, Y.-L. Zhang, C. Ko, S. Eusufzai, H. N. Ginsberg, and L.-S. Huang Post-transcriptional Stimulation of the Assembly and Secretion of Triglyceride-rich Apolipoprotein B Lipoproteins in a Mouse with Selective Deficiency of Brown Adipose Tissue, Obesity, and Insulin Resistance J. Biol. Chem., November 30, 2001; 276(49): 46064 - 46072. [Abstract] [Full Text] [PDF]

				V. A. Zammit, I. J. Waterman, D. Topping, and G. McKay Insulin Stimulation of Hepatic Triacylglycerol Secretion and the Etiology of Insulin Resistance J. Nutr., August 1, 2001; 131(8): 2074 - 2077. [Abstract] [Full Text] [PDF]

				M. Miyazaki, Y.-C. Kim, and J. M. Ntambi A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis J. Lipid Res., July 1, 2001; 42(7): 1018 - 1024. [Abstract] [Full Text] [PDF]

				R. A. Davis and T. Y. Hui 2000 George Lyman Duff Memorial Lecture : Atherosclerosis Is a Liver Disease of the Heart Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 887 - 898. [Abstract] [Full Text] [PDF]

				A. Carpentier, B. W. Patterson, K. D. Uffelman, A. Giacca, M. Vranic, M. S. Cattral, and G. F. Lewis The Effect of Systemic Versus Portal Insulin Delivery in Pancreas Transplantation on Insulin Action and VLDL Metabolism Diabetes, June 1, 2001; 50(6): 1402 - 1413. [Abstract] [Full Text]

				I. J. Goldberg Diabetic Dyslipidemia: Causes and Consequences J. Clin. Endocrinol. Metab., March 1, 2001; 86(3): 965 - 971. [Full Text]

				E. A. Fisher, M. Pan, X. Chen, X. Wu, H. Wang, H. Jamil, J. D. Sparks, and K. J. Williams The Triple Threat to Nascent Apolipoprotein B. EVIDENCE FOR MULTIPLE, DISTINCT DEGRADATIVE PATHWAYS J. Biol. Chem., July 20, 2001; 276(30): 27855 - 27863. [Abstract] [Full Text] [PDF]

				J.-s. Liang and H. N. Ginsberg Microsomal Triglyceride Transfer Protein Binding and Lipid Transfer Activities Are Independent of Each Other, but Both Are Required for Secretion of Apolipoprotein B Lipoproteins from Liver Cells J. Biol. Chem., July 20, 2001; 276(30): 28606 - 28612. [Abstract] [Full Text] [PDF]