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Apolipoprotein A-IV in the fed and fasting states.

To the Editor:

Apolipoprotein A-IV (apo A-IV) is a 46-kDa plasma protein (1) with different isoforms (2). It is secreted with chylomicrons into the circulation (3). Within the plasma compartment, apo A-IV dissociates from chylomicrons (4) and associates with HDL, triglyceride-rich lipoproteins, and the lipoprotein-free fraction (5).

Apo A-IV is influenced by dietary intervention, and a low-fat, low-cholesterol diet (NCEP Step II diet) and is able to decrease apo A-IV secretion rates significantly (6). Apo A-IV is catabolized rapidly with a fractional catabolic rate of ~2.4 pools/day (7). Apo A-IV is higher in patients with renal impairment (8). In ad-libitum-fed rats, serum apo A-IV concentrations showed a circadian rhythm associated with the feeding pattern (9). The role of apo A-IV as a risk indicator in coronary artery disease is currently unclear. Some studies have shown that apo A-IV concentrations are lower in patients with coronary artery disease (10), indicating that apo A-IV is an antiatherogenic protein. However, some questions remain unanswered because apo A-IV is also closely linked to several highly atherogenic situations in humans. For example, high triglyceride concentrations, renal impairment, or fat-enriched diets cause an increase in apo A-IV concentrations.


Because apo A-IV is linked to triglyceride concentrations, we were interested to study apo A-IV concentrations in the fasting and nonfasting state. We studied 28 normolipidemic healthy persons (13 men and 15 women; mean age, 30 years) with normal body weight for 24 h in the fasting and nonfasting states. Apo A-IV and lipoprotein concentrations were determined every 3 h for a total of 24 h by standard techniques as described recently (11). Each study sequence started at 0700 in the morning. For the fasting group, members were asked to skip their usual breakfast and remained fasting for at least 24 h. In contrast, for the nonfasting group, members were permitted to follow their typical food intake during the study. During prolonged fasting, the apo A-IV concentration decreased to ~50% of the starting concentration, from a mean (SD) of 150 (37) to 84 (26) mg/L (Fig. 1). Triglycerides decreased slightly, reaching a plateau within 6-12 h [decrease from 910 (370) to 750 (220) mg/L]. In the nonfasting state, apo A-IV concentrations were rather stable for 24 h, whereas triglycerides showed an increase over the daytime [between 1080 (530) and 1340 (690) mg/L], which correlated with apo A-IV (r = 0.238; P <0.01). We found no circadian rhythm of apo A-IV concentrations in our study participants; however, the decrease in apo A-IV plasma concentrations during extended fasting periods took surprisingly long. The usual 10- to 12-h fasting periods before blood drawing for lipid evaluations do not appear to be sufficient to reach baseline apo A-IV concentrations. Therefore, apo A-IV requires well-defined protocols when this protein is studied.

DOI: 10.1373/clinchem.2004.033001


(1.) Weinberg RB, Scanu AM. The isolation and characterization of human apolipoprotein A-IV from lipoprotein depleted serum. J Lipid Res 1983;24:52-9.

(2.) Schaefer JR, Hackler R, Brand S, Schwarz S, Kleine TO, Steinmetz A. Apolipoprotein AI, All, and AIV isoforms in plasma determined by automated isoelectric focusing with PhastSystem and immunofixation. Clin Chem 1995;41: 76-81.

(3.) Green PH, Glickman RM, Riley JW, Quinet E. Human apolipoprotein A-IV. Intestinal origin and distribution in plasma. J Clin Invest 1980;65: 911-9.

(4.) Fidge NH. The redistribution and metabolism of iodinated apolipoprotein A-IV in rats. Biochim Biophys Acta 1980;619:129-41.

(5.) Bisgaier CL, Sachdev OP, Megna L, Glickman RM. Distribution of apolipoprotein A-IV in human plasma. J Lipid Res 1985;26:11-25.

(6.) Sun Z, Welty FK, Dolnikowski GG, Lichtenstein AH, Schaefer EJ. Effects of a National Cholesterol Education Program Step II Diet on apolipoprotein A-IV metabolism within triacylglycerolrich lipoproteins and plasma. Am J Clin Nutr 2001;74:308-14.

(7.) Rader DJ, Schaefer JR, Lohse P, Verges B, Kindt M, Zech LA, et al. Rapid in vivo transport and catabolism of human apolipoprotein A-IV-1 and slower catabolism of the ApoA-IV-2 isoprotein. J Clin Invest 1993;92:1009-17.

(8.) Kronenberg F, Kuen E, Ritz E, K6nig P, Kraatz G, Lhotta K, et al. Apolipoprotein A-IV serum concentrations are elevated in patients with mild and moderate renal failure. J Am Soc Nephrol 2002;13:461-9.

(9.) Fukagawa k, Gou HM, Wolf R, Tso P. Circadian rhythm of serum and lymph apolipoprotein AIV in ad libitum-fed and fasted rats. Am J Physiol 1994;267:1385-90.

(10.) Kronenberg F, Struhlinger M, Trenkwalder E, Geethanjali FS, Pachinger 0, von Eckardstein A, et al. Low apolipoprotein A-IV plasma concentrations in men with coronary artery disease. J Am Coll Cardiol 2000;36:751-7.

(11.) Schwarz S, Haas B, Luley C, Schaefer JR, Steinmetz A. Quantification of apolipoprotein A-IV in human plasma by immunonephelometry. Clin Chem 1994;40:1717-21.

Alexander M. Sattler [1]

Rolf Hackler [1]

Mouhidien Soufi [1]

Armin Steinmetz [2]

Bernhard Maisch [1]

Juergen R. Schaefer [1] *

[1] Department of Internal Medicine


Philipps-University of Marburg

Marburg, Germany

[2] St. Nikolaus-Stiftshospital

* Address correspondence to this author at: Department of Internal MedicineCardiology, Philipps-University of Marburg, Baldinger Strasse, D-35033 Marburg, Germany. E-mail
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Title Annotation:Letters
Author:Rafat, Mostafa; Sattler, Alexander M.; Hackler,Rolf; Soufi, Mouhidien; Steinmetz, Armin; Maisch, Ber
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Jul 1, 2004
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