title: FABP4 plasma levels are increased in familial combined hyperlipidemia.
abstract: The lipid profile of familial combined hyperlipidemia (FCHL) shares some characteristics with atherogenic dyslipidemia seen in diabetes, metabolic syndrome, and obesity. Adipocyte fatty acid-binding protein 4 (FABP4) appears to be a determinant of atherogenic dyslipidemia. We examined relationships between FABP4 plasma concentrations, dyslipidemia, and metabolic variables in patients with FCHL. We studied 273 unrelated FCHL patients and 118 control subjects. FABP4 was higher in FCHL than controls, with mean levels of 21.8 (10.1) microg/l and 19.2 (9.2) microg/l, respectively (adjusted P= 0.012). In FCHL, FABP4 correlated to body mass index (BMI), waist circumference, insulin levels, and homeostasis model assessment (HOMA) index (all P< 0.05), but not to lipid levels, whereas in obese patients, FABP4 correlated to triglyceride levels (r = 0.303, P= 0.014) and very low density lipoprotein size (r = 0.502, P = 0.001), as determined by nuclear magnetic resonance. Associations of FABP4 with BMI and waist circumference, but not with insulin levels, persisted in this subgroup. Plasma FABP4 does not influence the lipid phenotype of FCHL. In a small subgroup of obese FCHL, FABP4 levels were associated with triglyceride-rich lipoproteins independent of insulin resistance. These results support a hyperlipidemic mechanism of FCHL different from similar metabolic conditions where fat mass is strongly related to FABP4 and hypertriglyceridemia.
authors.affiliation: Unitat de Recerca de Lípids i Arteriosclerosi, Universitat Rovira i Virgili, Servei de Medicina Interna, Hospital Universitari Sant Joan de Reus Reus, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: Cabré
authors.forename: Iolanda
authors.initials: I
authors.lastname: Lázaro
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cofán
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Jarauta
authors.forename: Núria
authors.initials: N
authors.lastname: Plana
authors.forename: Angel L
authors.initials: AL
authors.lastname: Garcia-Otín
authors.forename: Juan F
authors.initials: JF
authors.lastname: Ascaso
authors.forename: Raimón
authors.initials: R
authors.lastname: Ferré
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.forename: Lluís
authors.initials: L
authors.lastname: Masana
mesh_terms: D015331:Cohort Studies; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D006950:Hyperlipidemia, Familial Combined / Q000097:blood* / Q000453:epidemiology / Q000378:metabolism; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged
chemical_list: C493410:FABP4 protein, human; D050556:Fatty Acid-Binding Proteins
references.citation: Eur Heart J. 2008 Dec;29(24):2959-71
references.pmid: 18775919
references.citation: J R Soc Med. 2002;95 Suppl 42:46-53
references.pmid: 12216327
references.citation: Cell. 2008 Sep 19;134(6):933-44
references.pmid: 18805087
references.citation: Diabetes Care. 2007 Oct;30(10):2667-72
references.pmid: 17620449
references.citation: Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):167-74
references.pmid: 14551155
references.citation: AIDS. 2004 Mar 26;18(5):819-21
references.pmid: 15075521
references.citation: Circulation. 2007 Mar 27;115(12):1537-43
references.pmid: 17389279
references.citation: J Lipid Res. 2008 Aug;49(8):1746-51
references.pmid: 18421072
references.citation: Clin Chem. 2006 Mar;52(3):405-13
references.pmid: 16423904
references.citation: Atherosclerosis. 2008 Jul;199(1):147-53
references.pmid: 17983623
references.citation: Circulation. 2004 Sep 14;110(11):1492-8
references.pmid: 15353487
references.citation: Diabetologia. 1985 Jul;28(7):412-9
references.pmid: 3899825
references.citation: Circulation. 2004 Jun 15;109(23 Suppl 1):III2-7
references.pmid: 15198959
references.citation: FASEB J. 2005 Dec;19(14):2063-5
references.pmid: 16219805
references.citation: Diabetes. 2008 Aug;57(8):2022-7
references.pmid: 18469202
references.citation: J Lipid Res. 2005 Nov;46(11):2398-404
references.pmid: 16106049
references.citation: J Clin Invest. 1993 Feb;91(2):448-55
references.pmid: 8432854
references.citation: J Biol Chem. 2005 Apr 1;280(13):12888-95
references.pmid: 15684432
references.citation: Metabolism. 1976 Mar;25(3):313-20
references.pmid: 1250165
references.citation: Arterioscler Thromb. 1993 Jun;13(6):804-14
references.pmid: 8499400
references.citation: Atherosclerosis. 2007 Nov;195(1):e150-8
references.pmid: 17553506
references.citation: Eur J Clin Invest. 1980 Apr;10(2 Pt 1):161-72
references.pmid: 6780364
references.citation: Arterioscler Thromb Vasc Biol. 2007 Aug;27(8):1796-802
references.pmid: 17510463
references.citation: Circulation. 2004 Jan 27;109(3):433-8
references.pmid: 14744958
references.citation: Nat Med. 2001 Jun;7(6):699-705
references.pmid: 11385507
references.citation: Diabetes. 2006 Sep;55(9):2541-8
references.pmid: 16936202
references.citation: Am J Cardiol. 2003 Aug 18;92(4A):27J-33J
references.pmid: 12957324
references.citation: Metabolism. 1998 May;47(5):508-13
references.pmid: 9591739
references.citation: J Lipid Res. 2002 Jun;43(6):930-5
references.pmid: 12032168