PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jrsocmedLink to Publisher's site
 
J R Soc Med. 2002; 95(Suppl 42): 46–53.
PMCID: PMC1308945

Metabolic pathogenesis of familial combined hyperlipidaemia with emphasis on insulin resistance, adipose tissue metabolism and free fatty acids.

Full Text

The Full Text of this article is available as a PDF (115K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Goldstein JL, Schrott HG, Hazzard WR, Bierman EL, Motulsky AG. Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest. 1973 Jul;52(7):1544–1568. [PMC free article] [PubMed]
  • Rose HG, Kranz P, Weinstock M, Juliano J, Haft JI. Inheritance of combined hyperlipoproteinemia: evidence for a new lipoprotein phenotype. Am J Med. 1973 Feb;54(2):148–160. [PubMed]
  • Nikkilä EA, Aro A. Family study of serum lipids and lipoproteins in coronary heart-disease. Lancet. 1973 May 5;1(7810):954–959. [PubMed]
  • Bredie SJ, Demacker PN, Stalenhoef AF. Metabolic and genetic aspects of familial combined hyperlipidaemia with emphasis on low-density lipoprotein heterogeneity. Eur J Clin Invest. 1997 Oct;27(10):802–811. [PubMed]
  • de Graaf J, Stalenhoef AF. Defects of lipoprotein metabolism in familial combined hyperlipidaemia. Curr Opin Lipidol. 1998 Jun;9(3):189–196. [PubMed]
  • Aouizerat BE, Allayee H, Bodnar J, Krass KL, Peltonen L, de Bruin TW, Rotter JI, Lusis AJ. Novel genes for familial combined hyperlipidemia. Curr Opin Lipidol. 1999 Apr;10(2):113–122. [PubMed]
  • Veerkamp Mario J, de Graaf Jacqueline, Bredie Sebastian J H, Hendriks Jan C M, Demacker Pierre N M, Stalenhoef Anton F H. Diagnosis of familial combined hyperlipidemia based on lipid phenotype expression in 32 families: results of a 5-year follow-up study. Arterioscler Thromb Vasc Biol. 2002 Feb 1;22(2):274–282. [PubMed]
  • Sniderman AD, Castro Cabezas M, Ribalta J, Carmena R, de Bruin TWA, de Graaf J, Erkelens DW, Humphries SE, Masana L, Real JT, et al. A proposal to redefine familial combined hyperlipidaemia -- third workshop on FCHL held in Barcelona from 3 to 5 May 2001, during the scientific sessions of the European Society for Clinical Investigation. Eur J Clin Invest. 2002 Feb;32(2):71–73. [PubMed]
  • Venkatesan S, Cullen P, Pacy P, Halliday D, Scott J. Stable isotopes show a direct relation between VLDL apoB overproduction and serum triglyceride levels and indicate a metabolically and biochemically coherent basis for familial combined hyperlipidemia. Arterioscler Thromb. 1993 Jul;13(7):1110–1118. [PubMed]
  • Austin MA, Wijsman E, Guo SW, Krauss RM, Brunzell JD, Deeb S. Lack of evidence for linkage between low-density lipoprotein subclass phenotypes and the apolipoprotein B locus in familial combined hyperlipidemia. Genet Epidemiol. 1991;8(5):287–297. [PubMed]
  • Stalenhoef AF, Malloy MJ, Kane JP, Havel RJ. Metabolism of apolipoproteins B-48 and B-100 of triglyceride-rich lipoproteins in patients with familial dysbetalipoproteinemia. J Clin Invest. 1986 Sep;78(3):722–728. [PMC free article] [PubMed]
  • Babirak SP, Brown BG, Brunzell JD. Familial combined hyperlipidemia and abnormal lipoprotein lipase. Arterioscler Thromb. 1992 Oct;12(10):1176–1183. [PubMed]
  • Hoffer MJ, Bredie SJ, Boomsma DI, Reymer PW, Kastelein JJ, de Knijff P, Demacker PN, Stalenhoef AF, Havekes LM, Frants RR. The lipoprotein lipase (Asn291-->Ser) mutation is associated with elevated lipid levels in families with familial combined hyperlipidaemia. Atherosclerosis. 1996 Jan 26;119(2):159–167. [PubMed]
  • Pajukanta P, Porkka KV, Antikainen M, Taskinen MR, Perola M, Murtomäki-Repo S, Ehnholm S, Nuotio I, Suurinkeroinen L, Lahdenkari AT, et al. No evidence of linkage between familial combined hyperlipidemia and genes encoding lipolytic enzymes in Finnish families. Arterioscler Thromb Vasc Biol. 1997 May;17(5):841–850. [PubMed]
  • Saxena U, Witte LD, Goldberg IJ. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids. J Biol Chem. 1989 Mar 15;264(8):4349–4355. [PubMed]
  • Ong JM, Kirchgessner TG, Schotz MC, Kern PA. Insulin increases the synthetic rate and messenger RNA level of lipoprotein lipase in isolated rat adipocytes. J Biol Chem. 1988 Sep 15;263(26):12933–12938. [PubMed]
  • Ginsberg HN, Le NA, Goldberg IJ, Gibson JC, Rubinstein A, Wang-Iverson P, Norum R, Brown WV. Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo. J Clin Invest. 1986 Nov;78(5):1287–1295. [PMC free article] [PubMed]
  • Taskinen MR. Insulin resistance and lipoprotein metabolism. Curr Opin Lipidol. 1995 Jun;6(3):153–160. [PubMed]
  • Tchernof A, Lamarche B, Prud'Homme D, Nadeau A, Moorjani S, Labrie F, Lupien PJ, Després JP. The dense LDL phenotype. Association with plasma lipoprotein levels, visceral obesity, and hyperinsulinemia in men. Diabetes Care. 1996 Jun;19(6):629–637. [PubMed]
  • Bredie SJ, Tack CJ, Smits P, Stalenhoef AF. Nonobese patients with familial combined hyperlipidemia are insulin resistant compared with their nonaffected relatives. Arterioscler Thromb Vasc Biol. 1997 Jul;17(7):1465–1471. [PubMed]
  • Aitman TJ, Godsland IF, Farren B, Crook D, Wong HJ, Scott J. Defects of insulin action on fatty acid and carbohydrate metabolism in familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 1997 Apr;17(4):748–754. [PubMed]
  • Karjalainen L, Pihlajamäki J, Karhapä P, Laakso M. Impaired insulin-stimulated glucose oxidation and free fatty acid suppression in patients with familial combined hyperlipidemia: a precursor defect for dyslipidemia? Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1548–1553. [PubMed]
  • Pihlajamäki J, Karjalainen L, Karhapä P, Vauhkonen I, Laakso M. Impaired free fatty acid suppression during hyperinsulinemia is a characteristic finding in familial combined hyperlipidemia, but insulin resistance is observed only in hypertriglyceridemic patients. Arterioscler Thromb Vasc Biol. 2000 Jan;20(1):164–170. [PubMed]
  • Castro Cabezas M, de Bruin TW, de Valk HW, Shoulders CC, Jansen H, Willem Erkelens D. Impaired fatty acid metabolism in familial combined hyperlipidemia. A mechanism associating hepatic apolipoprotein B overproduction and insulin resistance. J Clin Invest. 1993 Jul;92(1):160–168. [PMC free article] [PubMed]
  • Hotamisligil GS, Arner P, Atkinson RL, Spiegelman BM. Differential regulation of the p80 tumor necrosis factor receptor in human obesity and insulin resistance. Diabetes. 1997 Mar;46(3):451–455. [PubMed]
  • Feingold KR, Serio MK, Adi S, Moser AH, Grunfeld C. Tumor necrosis factor stimulates hepatic lipid synthesis and secretion. Endocrinology. 1989 May;124(5):2336–2342. [PubMed]
  • Hauner H, Petruschke T, Russ M, Röhrig K, Eckel J. Effects of tumour necrosis factor alpha (TNF alpha) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture. Diabetologia. 1995 Jul;38(7):764–771. [PubMed]
  • Jacobson MS, Yoon DJ, Frank GR. Serum leptin is elevated out of proportion to the body mass index in adolescent females with familial combined hyperlipidemia (FCH). Clin Pediatr (Phila) 1999 Jan;38(1):49–53. [PubMed]
  • RANDLE PJ, GARLAND PB, HALES CN, NEWSHOLME EA. The glucose fatty-acid cycle. Its role in insulin sensitivity and the metabolic disturbances of diabetes mellitus. Lancet. 1963 Apr 13;1(7285):785–789. [PubMed]
  • Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest. 1995 Jan;95(1):158–166. [PMC free article] [PubMed]
  • Vakkilainen J, Porkka KV, Nuotio I, Pajukanta P, Suurinkeroinen L, Ylitalo K, Viikari JS, Ehnholm C, Taskinen MR. Glucose intolerance in familial combined hyperlipidaemia. EUFAM study group. Eur J Clin Invest. 1998 Jan;28(1):24–32. [PubMed]
  • Lamarche B. Abdominal obesity and its metabolic complications: implications for the risk of ischaemic heart disease. Coron Artery Dis. 1998;9(8):473–481. [PubMed]
  • Purnell JQ, Kahn SE, Schwartz RS, Brunzell JD. Relationship of insulin sensitivity and ApoB levels to intra-abdominal fat in subjects with familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 2001 Apr;21(4):567–572. [PubMed]
  • Juo SH, Bredie SJ, Kiemeney LA, Demacker PN, Stalenhoef AF. A common genetic mechanism determines plasma apolipoprotein B levels and dense LDL subfraction distribution in familial combined hyperlipidemia. Am J Hum Genet. 1998 Aug;63(2):586–594. [PubMed]
  • Van Harmelen V, Reynisdottir S, Cianflone K, Degerman E, Hoffstedt J, Nilsell K, Sniderman A, Arner P. Mechanisms involved in the regulation of free fatty acid release from isolated human fat cells by acylation-stimulating protein and insulin. J Biol Chem. 1999 Jun 25;274(26):18243–18251. [PubMed]
  • Sniderman AD, Cianflone K, Arner P, Summers LK, Frayn KN. The adipocyte, fatty acid trapping, and atherogenesis. Arterioscler Thromb Vasc Biol. 1998 Feb;18(2):147–151. [PubMed]
  • Cianflone KM, Sniderman AD, Walsh MJ, Vu HT, Gagnon J, Rodriguez MA. Purification and characterization of acylation stimulating protein. J Biol Chem. 1989 Jan 5;264(1):426–430. [PubMed]
  • Sniderman AD, Maslowska M, Cianflone K. Of mice and men (and women) and the acylation-stimulating protein pathway. Curr Opin Lipidol. 2000 Jun;11(3):291–296. [PubMed]
  • Cianflone KM, Maslowska MH, Sniderman AD. Impaired response of fibroblasts from patients with hyperapobetalipoproteinemia to acylation-stimulating protein. J Clin Invest. 1990 Mar;85(3):722–730. [PMC free article] [PubMed]
  • Zhang XJ, Cianflone K, Genest J, Sniderman AD. Plasma acylation stimulating protein (ASP) as a predictor of impaired cellular biological response to ASP in patients with hyperapoB. Eur J Clin Invest. 1998 Sep;28(9):730–739. [PubMed]
  • Wetsel RA, Kildsgaard J, Zsigmond E, Liao W, Chan L. Genetic deficiency of acylation stimulating protein (ASP(C3ades-Arg)) does not cause hyperapobetalipoproteinemia in mice. J Biol Chem. 1999 Jul 2;274(27):19429–19433. [PubMed]
  • Cianflone K, Zhang XJ, Genest J, Jr, Sniderman A. Plasma acylation-stimulating protein in coronary artery disease. Arterioscler Thromb Vasc Biol. 1997 Jul;17(7):1239–1244. [PubMed]
  • Ylitalo K, Pajukanta P, Meri S, Cantor RM, Mero-Matikainen N, Vakkilainen J, Nuotio I, Taskinen MR. Serum C3 but not plasma acylation-stimulating protein is elevated in Finnish patients with familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol. 2001 May;21(5):838–843. [PubMed]
  • Charlesworth JA, Peake PW, Campbell LV, Pussell BA, O'Grady S, Tzilopoulos T. The influence of oral lipid loads on acylation stimulating protein (ASP) in healthy volunteers. Int J Obes Relat Metab Disord. 1998 Nov;22(11):1096–1102. [PubMed]
  • Cianflone K, Vu H, Walsh M, Baldo A, Sniderman A. Metabolic response of Acylation Stimulating Protein to an oral fat load. J Lipid Res. 1989 Nov;30(11):1727–1733. [PubMed]
  • Saleh J, Summers LK, Cianflone K, Fielding BA, Sniderman AD, Frayn KN. Coordinated release of acylation stimulating protein (ASP) and triacylglycerol clearance by human adipose tissue in vivo in the postprandial period. J Lipid Res. 1998 Apr;39(4):884–891. [PubMed]
  • Reynisdottir S, Eriksson M, Angelin B, Arner P. Impaired activation of adipocyte lipolysis in familial combined hyperlipidemia. J Clin Invest. 1995 May;95(5):2161–2169. [PMC free article] [PubMed]
  • Ylitalo K, Large V, Pajukanta P, Reynisdottir S, Porkka KV, Vakkilainen J, Nuotio I, Taskinen MR, Arner P. Reduced hormone-sensitive lipase activity is not a major metabolic defect in Finnish FCHL families. Atherosclerosis. 2000 Dec;153(2):373–381. [PubMed]
  • Pihlajamäki J, Valve R, Karjalainen L, Karhapä P, Vauhkonen I, Laakso M. The hormone sensitive lipase gene in familial combined hyperlipidemia and insulin resistance. Eur J Clin Invest. 2001 Apr;31(4):302–308. [PubMed]
  • Arner P. Is familial combined hyperlipidaemia a genetic disorder of adipose tissue? Curr Opin Lipidol. 1997 Apr;8(2):89–94. [PubMed]
  • González-Manchón C, Martín-Requero A, Ayuso MS, Parrilla R. Role of endogenous fatty acids in the control of hepatic gluconeogenesis. Arch Biochem Biophys. 1992 Jan;292(1):95–101. [PubMed]
  • Meijssen S, Cabezas MC, Twickler TB, Jansen H, Erkelens DW. In vivo evidence of defective postprandial and postabsorptive free fatty acid metabolism in familial combined hyperlipidemia. J Lipid Res. 2000 Jul;41(7):1096–1102. [PubMed]

Articles from Journal of the Royal Society of Medicine are provided here courtesy of Royal Society of Medicine Press