Advertisement

Effects of gemfibrozil administration on very low density lipoprotein receptor mRNA levels in rabbits

      Abstract

      To elucidate the regulation of very low density lipoprotein (VLDL) receptor gene expression, we administered to rabbits for 14 days gemfibrozil, a fibric acid derivative and a lipid lowering drug that is also included among peroxisome proliferators. VLDL receptor mRNA levels were examined by Northern blot analysis. The VLDL receptor mRNA levels in retroperitoneal adipose tissue and in gastrocnemius muscle were increased 6.9-fold and 3.7-fold, respectively, with gemfibrozil treatment, but no marked changes were observed in the heart, the organ in which VLDL receptor is most highly expressed. In the liver, VLDL receptor mRNA was not detected either before or after gemfibrozil administration. Lipoprotein lipase (LPL) and long-chain acyl coenzyme A synthetase (ACS) mRNA levels were also increased in parallel in adipose tissue. The enhanced expression of VLDL receptor mRNA may contribute to the increase of triglyceride-rich lipoprotein catabolism in peripheral tissues such as adipose tissue and muscles.

      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

        • Takahashi S
        • Kawarabayasi Y
        • Nakai T
        • Sakai J
        • Yamamoto T
        Rabbit very low density lipoprotein receptor: a low density lipoprotein receptor-like protein with distinct ligand specificity.
        Proc Natl Acad Sci USA. 1992; 89: 9252-9256
        • Gåfvels ME
        • Caird M
        • Britt D
        • Jackson CL
        • Patterson D
        • Strauss III, JF
        Cloning of a cDNA encoding a putative human very low density lipoprotein/apolipoprotein E receptor and assignment of the gene to chromosome 9pter-p23.
        Somat Cell Mol Genet. 1993; 19: 557-569
        • Sakai J
        • Hoshino A
        • Takahashi S
        • et al.
        Structure, chromosome location, and expression of the human very low density lipoprotein receptor gene.
        J Biol Chem. 1994; 269: 2173-2182
        • Jokinen EV
        • Landschulz KT
        • Wyne KL
        • Ho YK
        • Frykman PK
        • Hobbs HH
        Regulation of the very low density lipoprotein receptor by thyroid hormone in rat skeletal muscle.
        J Biol Chem. 1994; 269: 26411-26418
        • Oka K
        • Ishimura-Oka K
        • Chu M
        • et al.
        Mouse very-low-density-lipoprotein receptor (VLDLR) cDNA cloning, tissue-specific expression and evolutionary relationship with the low-density-lipoprotein receptor.
        Eur J Biochem. 1994; 224: 975-982
        • Webb JC
        • Patel DD
        • Jones MD
        • Knight BL
        • Soutar AK
        Characterization and tissue-specific expression of the human ‘very low density lipoprotein (VLDL) receptor‘ mRNA.
        Hum Mol Genet. 1994; 3: 531-537
        • Gåfvels ME
        • Paavola LG
        • Boyd CO
        • et al.
        Cloning of a complementary deoxyribonucleic acid encoding the murine homolog of the very low density lipoprotein/apolipoprotein-E receptor: expression pattern and assignment of the gene to mouse chromosome 19.
        Endocrinology. 1994; 135: 387-394
        • Bujo H
        • Hermann M
        • Kaderli MO
        • et al.
        Chicken oocyte growth is mediated by an eight ligand binding repeat member of the LDL receptor family.
        EMBO J. 1994; 13: 5165-5175
        • Jingami H
        • Yamamoto T
        The VLDL receptor: wayward brother of the LDL receptor.
        Curr Opin Lipidol. 1995; 6: 104-108
        • Yamamoto T
        • Hoshino A
        • Takahashi S
        • Kawarabayasi Y
        • Iijima H
        • Sakai J
        The role of the very low density lipoprotein receptor in the metabolism of plasma lipoproteins containing apoE.
        Ann NY Acad Sci. 1995; 748: 217-225
        • Herz J
        • Hamann U
        • Rogne S
        • Myklebost O
        • Gausepohl H
        • Stanley KK
        Surface location and high affinity of calcium of a 500-kD liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor.
        EMBO J. 1988; 7: 4119-4127
        • Schonbaum CP
        • Lee S
        • Mahowald AP
        The Drosophila yolkless gene encodes a vitellogenin receptor belonging to the low density lipoprotein receptor superfamily.
        Proc Natl Acad Sci USA. 1995; 92: 1485-1489
        • Simonsen ACW
        • Heegaard CW
        • Rasmussen LK
        • et al.
        Very low density lipoprotein receptor from mammary gland and mammary epithelial cell lines binds and mediates endocytosis of Mr 40 000 receptor associated protein.
        FEBS lett. 1994; 354: 279-283
        • Battey FD
        • Gåfvels ME
        • FitzGerald DJ
        • et al.
        The 39-kDa receptor-associated protein regulates ligand binding by the very low density lipoprotein receptor.
        J Biol Chem. 1994; 269: 23268-23273
        • Suzuki J
        • Takahashi S
        • Oida K
        • et al.
        Lipid accumulation and foam cell formation in Chinese Hamster ovary cells overexpressing very low density lipoprotein receptor.
        Biochem Biophys Res Commun. 1995; 206: 835-842
        • Wittmaack FM
        • Gåfvels ME
        • Bronner M
        • et al.
        Localization and regulation of the human very low density lipoprotein/apolipoprotein-E receptor: trophoblast expression predicts a role for the receptor in placental lipid transport.
        Endocrinology. 1995; 136: 340-348
        • Masuzaki H
        • Jingami H
        • Yamamoto T
        • Nakao K
        Effects of estradiol on very low density lipoprotein receptor mRNA levels in rabbit heart.
        FEBS Lett. 1994; 347: 211-214
        • Ishibashi T
        • Yokoyama K
        • Shindo J
        • et al.
        Potent cholesterol-lowering effect of human granulocyte-macrophage colony-stimulating factor in rabbits: possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor.
        Arterioscler Thromb. 1994; 14: 1534-1541
        • Simsolo RB
        • Ong JM
        • Kern PA
        Effect of gemfibrozil on adipose tissue and muscle lipoprotein lipase.
        Metabolism. 1993; 42: 1486-1491
        • Larsen ML
        • Illingworth DR
        • O'Malley JP
        Comparative effects of gemfibrozil and clofibrate in type III hyperlipoproteinemia.
        Atherosclerosis. 1994; 106: 235-240
        • Todd PA
        • Ward A
        Gemfibrozil: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in dyslipidaemia.
        Drugs. 1988; 36: 314-339
        • Rodney G
        • Uhlendorf P
        • Maxwell RE
        The hypolipidaemic effect of gemfibrozil (CI-719) in laboratory animals.
        Proc R Soc Med. 1976; 69: 6-10
        • Issmann I
        • Green S
        Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators.
        Nature. 1990; 347: 645-650
        • Frick MH
        • Elo O
        • Haapa K
        • et al.
        Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia.
        N Engl J Med. 1987; 317: 1237-1245
        • Chomczynski P
        • Sacchi N
        Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction.
        Anal Biochem. 1987; 162: 156-159
        • Masuzaki H
        • Ogawa Y
        • Isse N
        • et al.
        Human Obese gene expression; adipocyte-specific expression and regional differences in the adipose tissue.
        Diabetes. 1995; 44: 855-858
        • Yamamoto T
        • Bishop RW
        • Brown MS
        • Goldstein JL
        • Russell DW
        Deletion in cysteine-rich region of LDL receptor impedes transport to cell surface in WHHL rabbit.
        Science. 1986; 232: 1230-1237
        • Suzuki H
        • Kawarabayasi Y
        • Kondo J
        • et al.
        Structure and regulation of rat long-chain acyl-CoA synthetase.
        J Biol Chem. 1990; 265: 8681-8685
        • Wion KL
        • Kirchgessner TG
        • Lusis AJ
        • Schotz MC
        • Lawn RM
        Human lipoprotein lipase complementary DNA sequence.
        Science. 1987; 235: 1638-1641
        • Harris DE
        • Warshaw DM
        • Periasamy M
        Nucleotide sequences of the rabbit α-smooth-muscle and β-non-muscle actin mRNAs.
        Gene. 1992; 112: 265-266
        • Schoonjans K
        • Staels B
        • Grimaldi P
        • Auwerx J
        Acyl-CoA synthetase mRNA expression is controlled by fibric-acid derivatives, feeding and liver proliferation.
        Eur J Biochem. 1993; 2116: 615-622