title: Independent Link Between Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and FABP4 in a General Population Without Medication.
abstract: Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to and degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Fatty acid binding protein 4 (FABP4/adipocyte FABP/aP2) is secreted from adipocytes in association with lipolysis, and circulating FABP4 has been reported to act as an adipokine for the development of insulin resistance and atherosclerosis. Elevated serum FABP4 level is associated with obesity, insulin resistance, dyslipidemia, and atherosclerosis. In this study, we examined the association between circulating levels of FABP4 and PCSK9 in a general population. A total of 265 subjects (male/female: 98/167) who were not on medication were recruited from subjects of the Tanno-Sobetsu Study, and concentrations of FABP4 and PCSK9 were measured. The level of FABP4, but not that of PCSK9, showed a gender difference, being higher in women than in men. FABP4 level was independently associated with gender, adiposity, renal dysfunction, and levels of cholesterol and PCSK9. There was a significant and gender-different correlation between PCSK9 level and age: negatively in men (r = -0.250, p = 0.013) and positively in women (r = 0.183, p = 0.018). After adjustment of age, gender, and LDL cholesterol level, PCSK9 level was positively and independently correlated with FABP4 concentration. In conclusion, PCSK9 level is differentially regulated by gender during aging. Circulating FABP4 is independently associated with the PCSK9 level, suggesting that elevation of FABP4 level as an adipokine leads to dyslipidemia through increased PCSK9 level and subsequent degradation of the LDL receptor.
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan. Electronic address: furuhasi@sapmed.ac.jp.
authors.forename: Masato
authors.initials: M
authors.lastname: Furuhashi
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Akina
authors.initials: A
authors.lastname: Omori
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Kataoka
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Marenao
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Moniwa
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan; Department of Public Health, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohnishi
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yoshida
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan; Division of Medical and Behavioral Subjects, Department of Nursing, Sapporo Medical University School of Health Sciences, Sapporo, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Saitoh
authors.affiliation: Sapporo Medical University, Sapporo, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Shimamoto
authors.affiliation: Department of Cardiovascular, Renal and Metabolic Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
authors.forename: Tetsuji
authors.initials: T
authors.lastname: Miura
mesh_terms: D000367:Age Factors; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D002097:C-Reactive Protein / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003404:Creatinine / Q000097:blood; D050171:Dyslipidemias / Q000097:blood* / Q000453:epidemiology; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000097:blood* / Q000453:epidemiology; D000071449:Proprotein Convertase 9 / Q000097:blood*; D012044:Regression Analysis; D012737:Sex Factors; D014280:Triglycerides / Q000097:blood; D014527:Uric Acid / Q000097:blood; D055105:Waist Circumference; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D002097:C-Reactive Protein; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D003404:Creatinine; D050556:Fatty Acid-Binding Proteins; D006442:Glycated Hemoglobin; D000071449:Proprotein Convertase 9; D014280:Triglycerides; D014527:Uric Acid; D005723:gamma-Glutamyltransferase; C493410:FABP4 protein, human; C517652:hemoglobin A1c protein, human; C554782:gamma-glutamyltransferase, human; C472125:PCSK9 protein, human