title: Apolipoprotein A-I, B-100, and B-48 metabolism in subjects with chronic kidney disease, obesity, and the metabolic syndrome.
abstract: The metabolism of apolipoproteins (apo)B-48, B-100, and A-I was studied with a primed constant infusion of deuterium-labeled leucine in the fed state in 3 male individuals with chronic kidney disease (CKD), a glomerular filtration rate (GFR) of 28 to 57 mL/min/1.73 m2, obesity (body mass index [BMI] 33.1), and the metabolic syndrome. Compared to 5 obese controls (BMI 30.1) and 13 non-obese controls (BMI 25.2), these CKD subjects had high plasma levels of triglycerides (TG) (343 +/- 27.5 mg/dL v 144 +/- 34.4 in the obese controls, P < .001) and low apoA-I (86.7 +/- 3.9 mg/dL). An abnormal high-density lipoprotein (HDL) particle subpopulation pattern was found, with low levels of pre beta-1 and alpha1. Compared to the obese controls, very-low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) apoB-100 levels were elevated 2- to 3-fold, while LDL apoB-100 levels were slightly lower (-7 %) and apoB-48 levels were comparable. The high TG levels were not associated with statistically significant changes in VLDL apoB-100 kinetics, although the production rate (PR) was higher and the fractional catabolic rate (FCR) was lower. The slightly lower LDL apoB-100 levels were accompanied by a significant 3-fold increase in the FCR and a 2.7-fold increase in the PR. The lower apoA-I levels were accompanied by a 1.6-fold increase in the FCR. Compared to the non-obese controls, the PR of apoA-I was increased by 61% and 38%, respectively (P < .001) in CKD and in obese control subjects. In the control subjects, the PR of apoA-I was significantly correlated with the BMI (r = 0.81, P < .0001). The kinetic results are consistent with these hypotheses: (1) CKD is associated with decreased clearance of the TG-rich lipoproteins (TRLs) and increased catabolism of LDL; (2) obesity increases apoB-100 and apoA-I production; and (3) in CKD, TG transfer to HDL, making HDL more susceptible to catabolism, accounts for the low apoA-I levels.
authors.affiliation: Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA.
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Batista
authors.forename: Francine K
authors.initials: FK
authors.lastname: Welty
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Diffenderfer
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Sarnak
authors.forename: Ernst J
authors.initials: EJ
authors.lastname: Schaefer
authors.forename: Stefania
authors.initials: S
authors.lastname: Lamon-Fava
authors.forename: Bela F
authors.initials: BF
authors.lastname: Asztalos
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Dolnikowski
authors.forename: Margaret E
authors.initials: ME
authors.lastname: Brousseau
authors.forename: Julian B
authors.initials: JB
authors.lastname: Marsh
mesh_terms: D000368:Aged; D016632:Apolipoprotein A-I / Q000378:metabolism*; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D002908:Chronic Disease; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D006949:Hyperlipidemias / Q000209:etiology; D007674:Kidney Diseases / Q000150:complications / Q000378:metabolism*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism*; D008875:Middle Aged; D008954:Models, Biological; D009765:Obesity / Q000150:complications / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D053299:Apolipoprotein B-100; D053283:Apolipoprotein B-48; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D008074:Lipoproteins; D002784:Cholesterol