Advertisement

Visceral obesity and hyperinsulinemia modulate the impact of the microsomal triglyceride transfer protein −493G/T polymorphism on plasma lipoprotein levels in men

  • Julie St-Pierre
    Affiliations
    Dyslipidemia, Diabetes and Atherosclerosis Group, Complexe Hospitalier de la Sagamie, Chicoutimi Que., Canada G7H 5H6

    Lipid Research Center, Laval University Medical Research Center, CHUQ, Pavilion CHUL, 2705, Laurier Boulevard, Room RC-9500, Sainte-Foy Que., Canada G1V-4G2
    Search for articles by this author
  • Isabelle Lemieux
    Affiliations
    Lipid Research Center, Laval University Medical Research Center, CHUQ, Pavilion CHUL, 2705, Laurier Boulevard, Room RC-9500, Sainte-Foy Que., Canada G1V-4G2
    Search for articles by this author
  • Isabelle Miller-Felix
    Affiliations
    Lipid Research Center, Laval University Medical Research Center, CHUQ, Pavilion CHUL, 2705, Laurier Boulevard, Room RC-9500, Sainte-Foy Que., Canada G1V-4G2

    Department of Food Sciences and Nutrition, Laval University, Sainte-Foy Que., Canada G1K 7P4
    Search for articles by this author
  • Denis Prud'homme
    Affiliations
    Lipid Research Center, Laval University Medical Research Center, CHUQ, Pavilion CHUL, 2705, Laurier Boulevard, Room RC-9500, Sainte-Foy Que., Canada G1V-4G2

    Division of Kinesiology, Faculty of Medicine, Laval University, Canada
    Search for articles by this author
  • Jean Bergeron
    Affiliations
    Lipid Research Center, Laval University Medical Research Center, CHUQ, Pavilion CHUL, 2705, Laurier Boulevard, Room RC-9500, Sainte-Foy Que., Canada G1V-4G2
    Search for articles by this author
  • Daniel Gaudet
    Affiliations
    Dyslipidemia, Diabetes and Atherosclerosis Group, Complexe Hospitalier de la Sagamie, Chicoutimi Que., Canada G7H 5H6
    Search for articles by this author
  • André Nadeau
    Affiliations
    Diabetes Research Unit, Laval University Medical Research Center, Sainte-Foy Que., Canada G1V 4G2
    Search for articles by this author
  • Jean-Pierre Després
    Affiliations
    Lipid Research Center, Laval University Medical Research Center, CHUQ, Pavilion CHUL, 2705, Laurier Boulevard, Room RC-9500, Sainte-Foy Que., Canada G1V-4G2

    Department of Food Sciences and Nutrition, Laval University, Sainte-Foy Que., Canada G1K 7P4

    Quebec Heart Institute, Laval Hospital Research Center, Sainte-Foy Que., Canada G1V 4G5
    Search for articles by this author
  • Marie-Claude Vohl
    Correspondence
    Corresponding author. Tel.: +1-418-654-2133; fax: +1-418-654-2176
    Affiliations
    Lipid Research Center, Laval University Medical Research Center, CHUQ, Pavilion CHUL, 2705, Laurier Boulevard, Room RC-9500, Sainte-Foy Que., Canada G1V-4G2

    Department of Food Sciences and Nutrition, Laval University, Sainte-Foy Que., Canada G1K 7P4
    Search for articles by this author

      Abstract

      The dyslipidemic state of visceral obesity is characterized by increased plasma triglyceride levels, low high-density lipoprotein-cholesterol concentration and alterations in low-density lipoprotein (LDL) composition and concentration. A functional, non-coding microsomal triglyceride transfer protein (MTP) −493G/T polymorphism of the microsomal triglyceride transfer protein gene has been related to variations in LDL-cholesterol levels. To study the effect of the MTP −493G/T polymorphism on lipoprotein levels in visceral obesity and hyperinsulinemia, a total of 227 men were assigned into two groups on the basis of their MTP −493G/T polymorphism, including 121 GG homozygotes and 105 carriers of the T allele (92 GT and 13 TT). The two genotypic groups did not differ for their physiological characteristics nor for lipoprotein–lipid profiles, before and after adjustment for age. However, GG homozygotes were characterized by higher fasting insulin levels than carriers of the T allele (P<0.05). When the two genotypic groups were further divided on the basis of their visceral adipose tissue (AT) accumulation, assessed by computed tomography, we observed that T allele carriers with low levels of visceral AT (<130 cm2) had decreased plasma total cholesterol and LDL-apolipoprotein B (LDL-apoB) levels compared to viscerally obese men (P=0.035 and P=0.0001, respectively). Among GG homozygotes, no significant difference were observed. Although not significant, T allele carriers characterized by visceral obesity tended to have smaller, denser LDL particles than T allele carriers characterized by a low accumulation of visceral AT. When subjects were divided on the basis of their fasting insulin levels, it appears that hyperinsulinemic men were characterized by a deteriorated lipoprotein–lipid profile when they were carriers of the T allele compared to normoinsulinemic men. In summary, visceral obesity and hyperinsulinemia modulate the impact of the MTP −493G/T polymorphism on plasma total cholesterol and LDL-apoB levels, as well as on LDL peak particle diameter.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Després J.P
        • Moorjani S
        • Lupien P.J
        • Tremblay A
        • Nadeau A
        • Bouchard C
        Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease.
        Arteriosclerosis. 1990; 10: 497-511
      1. Kissenbah AH, Krakower GR. Regional adiposity and morbidity. Physiol Rev 1994;74:761–811.

        • Pouliot M.C
        • Després J.P
        • Nadeau A
        • Moorjani S
        • Prud'homme D
        • Lupien P.J
        • et al.
        Visceral obesity in men. Associations with glucose tolerance, plasma insulin, and lipoprotein levels.
        Diabetes. 1992; 41: 826-834
        • Lamarche B
        • Després J.P
        • Moorjani S
        • Cantin B
        • Dagenais G.R
        • Lupien P.J
        Prevalence of dyslipidemic phenotypes in ischemic heart disease.
        Am J Cardiol. 1995; 75: 1189-1195
        • Tchernof A
        • Lamarche B
        • Prud'Homme D
        • Nadeau A
        • Moorjani S
        • Labrie F
        • et al.
        The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men.
        Diab Care. 1996; 19: 629-637
        • Miller B.D
        • Alderman E.L
        • Haskell W.L
        • Fair J.M
        • Krauss R.M
        Predominance of dense low-density lipoprotein particles predicts angiographic benefit of therapy in the Stanford Coronary Risk Intervention Project.
        Circulation. 1996; 94: 2146-2153
        • Stampfer M.J
        • Krauss R.M
        • Ma J
        • Blanche P.J
        • Holl L.G
        • Sacks F.M
        • et al.
        A prospective study of triglyceride level, low-density lipoprotein particle diameter, andrisk of myocardial infarction.
        JAMA. 1996; 276: 882-888
        • Lamarche B
        • Tchernof A
        • Moorjani S
        • Cantin B
        • Dagenais G.R
        • Lupien P.J
        • et al.
        Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study.
        Circulation. 1997; 95: 69-75
        • Wetterau J.R
        • Combs K.A
        • Spinner S.N
        • Joiner B.J
        Protein disulfide isomerase is a component of the microsomal triglyceride transfer protein complex.
        J Biol Chem. 1990; 265: 9801-9807
        • Sharp D
        • Blinderman L
        • Combs K.A
        • Kienzle B
        • Ricci B
        • Wager-Smith K
        • et al.
        Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia.
        Nature. 1993; 365: 65-69
        • Ricci B
        • Sharp D
        • O'Rourke E
        • Kienzle B
        • Blinderman L
        • Gordon D
        • et al.
        A 30-amino acid truncation of the microsomal triglyceride transfer protein large subunit disrupts its interaction with protein disulfide-isomerase and causes abetalipoproteinemia.
        J Biol Chem. 1995; 270: 14281-14285
        • Narcisi T.M
        • Shoulders C.C
        • Chester S.A
        • Read J
        • Brett D.J
        • Harrison G.B
        • et al.
        Mutations of the microsomal triglyceride-transfer-protein gene in abetalipoproteinemia.
        Am J Hum Genet. 1995; 57: 1298-1310
        • Yang X.P
        • Inazu A
        • Yagi K
        • Kajinami K
        • Koizumi J
        • Mabuchi H
        Abetalipoproteinemia caused by maternal isodisomy of chromosome 4q containing an intron 9 splice acceptor mutation in the microsomal triglyceride transfer protein gene.
        Arterioscler Thromb Vasc Biol. 1999; 19: 1950-1955
        • Karpe F
        • Lundahl B
        • Ehrenborg E
        • Eriksson P
        • Hamsten A
        A common functional polymorphism in the promoter region of the microsomal triglyceride transfer protein gene influences plasma LDL levels.
        Arterioscler Thromb Vasc Biol. 1998; 18: 756-761
        • Ferland M
        • Després J.P
        • Tremblay A
        • Pinault S
        • Nadeau A
        • Moorjani S
        • et al.
        Assessment of adipose tissue distribution by computed axial tomography in obese women: association with body density and anthropometric measurements.
        Br J Nutr. 1989; 61: 139-148
      2. Standardization of anthropometric measurements. In: Lohman T, Roche A, Martorel R, editors. The Airlie (VA) Consensus Conference. Human kinetics, p. 39–80.

        • Richterich R
        • Dauwalder H
        Zur bestimmung der plasmagluko-sekonzentration mit der hexokinase-glucose-6-phosphat-dehydroghenase-method.
        Scheiwz Med Wochenschr. 1971; 101: 615-618
        • Desbuquois B
        • Aurbach G.D
        Use of polyethylene glycol to separate free and anibody-bound peptids hormones in radioimmunoassays.
        J Clin Endocrinol Metab. 1971; 37: 732-738
        • Havel R.J
        • Eder H.A
        • Bragdon J.H
        The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum.
        J Clin Invest. 1955; 34: 1345-1354
        • Burstein M
        • Samaille J
        Quick dosage of cholesterol linked to plasma α and β-lipoproteins.
        Clin Chim Acta. 1960; 5: 609-610
        • Gidez L.I
        • Miller G.J
        • Burstein M
        • Slagle S
        • Eder H.A
        Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure.
        J Lipid Res. 1982; 23: 1206-1223
        • Laurell C.B
        Quantitative estimation of proteins by electrophoresis in agarose gel containing antibodies.
        Ann Biochem. 1966; 15: 45-52
        • Moorjani S
        • Dupont A
        • Labrie F
        • Lupien P.J
        • Brun D
        • Gagné C
        • et al.
        Increase in plasma high-density lipoprotein concentration following complete androgen blockage in men with prostatic carcinoma.
        Metabolism. 1987; 36: 244-250
        • Krauss R.M
        • Burke D.J
        Identification of multiple subclasses of plasma low density lipoproteins in normal humans.
        J Lipid Res. 1982; 23: 97-104
        • McNamara J.R
        • Campos H
        • Ordovas J.M
        • Peterson J
        • Wilson P.W
        • Schaefer E.J
        Effect of gender, age, and lipid status on low density lipoprotein subfraction distribution. Results from the Framingham Offspring Study.
        Arteriosclerosis. 1987; 7: 483-490
        • Després J.P
        • Lamarche B
        Effects of diet and physical activity on adipose and body fat distribution: implications for the prevention of cardiovascular disease.
        Nutr Res Rev. 1993; 113: 151-169
        • Lemieux S
        • Prud'homme D
        • Bouchard C
        • Tremblay A
        • Després J.P
        A single threshold value of waist girth identifies normal-weight and overweight subjects with excess visceral adipose tissue.
        Am J Clin Nutr. 1996; 64: 685-693
        • Pouliot M.C
        • Després J.P
        • Lemieux S
        • Moorjani S
        • Bouchard C
        • Tremblay A
        • et al.
        Waist circumference and abdominal sagittal indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women.
        Am J Cardiol. 1994; 73: 460-468
        • Julien P
        • Vohl M.C
        • Gaudet D
        • Gagné C
        • Lévesque G
        • Després J.P
        • et al.
        Hyperinsulinemia and abdominal obesity affect the expression of hypertriglyceridemia in heterozygous familial lipoprotein lipase deficiency.
        Diabetes. 1997; 46: 2063-2068
        • Vohl M.C
        • Lamarche B
        • Bergeron J
        • Moorjani S
        • Prud'homme D
        • Nadeau A
        • et al.
        The MspI polymorphism of the apolipoprotein A-II gene as a modulator of the dyslipidemic state found in visceral obesity.
        Atherosclerosis. 1997; 128: 183-190
        • Davignon J
        • Genest Jr, J
        Genetics of lipoprotein disorders.
        Endocrinol Metab Clin North Am. 1998; 27: 521-550
      3. Vohl MC, Lepage P, Gaudet D, Brewer CG, Bétard C, Perron P, et al. Molecular scanning of the human PPARα gene: association of the L162V mutation with hyperapobetalipoproteinemia. J Lipid Res 2000;41:945–52.

        • Després J.P
        • Verdon M.F
        • Moorjani S
        • Pouliot M.C
        • Nadeau A
        • Bouchard C
        • et al.
        Apolipoprotein E polymorphism modifies relation of hyperinsulinemia to hypertriglyceridemia.
        Diabetes. 1993; 42: 1474-1481
        • Pouliot M.C
        • Després J.P
        • Moorjani S
        • Lupien P.J
        • Tremblay A
        • Bouchard C
        Apolipoprotein E polymorphism alters the association between body fatness and plasma lipoproteins in women.
        J Lipid Res. 1990; 31: 1023-1029
        • Pouliot M.C
        • Després J.P
        • Dionne F.T
        • Vohl M.C
        • Moorjani S
        • Prud'homme D
        • et al.
        ApoB-100 gene EcoRI polymorphism. Relations to plasma lipoprotein changes associated with abdominal visceral obesity.
        Arterioscler Thromb. 1994; 14: 527-533
        • Vohl M.C
        • Lamarche B
        • Pascot A
        • Leroux G
        • Prud'homme D
        • Bouchard C
        • et al.
        Contribution of the cholesteryl ester transfer protein gene TaqIB polymorphism to the reduced plasma HDL-cholesterol levels found in abdominal obese men with the features of the insulin resistance syndrome.
        Int J Obes Relat Metab Disord. 1999; 23: 918-925
        • Vohl M.C
        • Lamarche B
        • Moorjani S
        • Prud'homme D
        • Nadeau A
        • Bouchard C
        • et al.
        The lipoprotein lipase HindIII polymorphism modulates plasma triglyceride levels in visceral obesity.
        Arterioscler Thromb Vasc Biol. 1995; 15: 714-720
        • Couture P
        • Otvos J.D
        • Cupples L.A
        • Wilson P.W
        • Schaefer E.J
        • Ordovas J.M
        Absence of association between genetic variation in the promoter of the microsomal triglyceride transfer protein gene and plasma lipoproteins in the Framingham Offspring Study.
        Atherosclerosis. 2000; 148: 337-343
        • Gordon D.A
        • Jamil H
        • Sharp D
        • Mullaney D
        • Yao Z
        • Gregg R.E
        • et al.
        Secretion of apolipoprotein B-containing lipoproteins from HeLa cells is dependent on expression of the microsomal triglyceride transfer protein and is regulated by lipid availability.
        Proc Natl Acad Sci USA. 1994; 91: 7628-7632
        • Leiper J.M
        • Bayliss J.D
        • Pease R.J
        • Brett D.J
        • Scott J
        • Shoulders C.C
        Microsomal triglyceride transfer protein, the abetalipoproteinemia gene product, mediates the secretion of apolipoprotein B-containing lipoproteins from heterologous cells.
        J Biol Chem. 1994; 269: 21951-21954
        • Tietge U.J
        • Bakillah A
        • Maugeais C
        • Tsukamoto K
        • Hussain M
        • Rader D.J
        Hepatic overexpression of microsomal triglyceride transfer protein (MTP) results in increased in vivo secretion of VLDL triglycerides and apolipoprotein B.
        J Lipid Res. 1999; 40: 2134-2139