QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kratz, M. Articles by Kronenberg, F. Search for Related Content PubMed PubMed Citation Articles by Kratz, M. Articles by Kronenberg, F.

---

Human Nutrition and Metabolism

Dietary Mono- and Polyunsaturated Fatty Acids Similarly Increase Plasma Apolipoprotein A-IV Concentrations in Healthy Men and Women

Mario Kratz², Ursel Wahrburg^*, Arnold von Eckardstein, Benjie Ezeh^**, Gerd Assmann and Florian Kronenberg^**,

Institute of Arteriosclerosis Research at the University of Münster, 48149 Münster, Germany; ^* University of Applied Sciences, 48151 Münster, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University of Zürich, 8091 Zürich, Switzerland; ^** Institute of Medical Biology and Human Genetics, University of Innsbruck, 6020 Innsbruck, Austria; GSF-National Research Center for Environment and Health, Institute of Epidemiology, 85764 Neuherberg, Germany

²To whom correspondence and reprint requests should be addressed. E-mail: mkratz{at}uni-muenster.de.

	ABSTRACT

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
We investigated the effect of dietary fatty acid composition on plasma apolipoprotein (apo) A-IV concentrations. Plasma apo A-IV concentrations were measured by ELISA in plasma of 48 healthy men and women in a controlled dietary study. First, all participants consumed a 2-wk baseline diet rich in saturated fatty acids (SFA). Then, they were randomly assigned to one of three dietary treatments, which contained refined olive oil [rich in monounsaturated fatty acids (MUFA), n = 17], rapeseed oil {rich in MUFA and -linolenic acid [18:3(n-3)], n = 13}, or sunflower oil [rich in (n-6) PUFA, n = 18] as the principal source of fat for 4 wk. The plasma concentrations of apo A-IV increased when subjects consumed the diets rich in unsaturated fatty acids, by 16% or 13.0 mg/L [F_(2,76) = 12.874, P < 0.001 by repeated-measures ANOVA]. The increase was not affected by diet group affiliation, gender or apo A-IV genotype. In conclusion, diets rich in unsaturated fatty acids, independent of the degree of unsaturation, gender and apo A-IV genotype, increase plasma apo A-IV concentrations compared with a baseline diet rich in SFA in healthy men and women.

KEY WORDS: • monounsaturated fatty acids • polyunsaturated fatty acids • chylomicrons • absorption • humans

Human apolipoprotein (apo) A-IV is a 46-kDa glycoprotein (1, 2) that is synthesized in the small intestine in response to the absorption of dietary or biliary fat. Apo A-IV synthesis is likely coupled to the assembly and/or transport of chylomicrons (3). Apo A-IV reaches the bloodstream as part of the chylomicrons via the thoracic duct, and is present in plasma either bound to HDL or in a free form (4,5). Numerous in vitro studies suggest that apo A-IV participates in the reverse cholesterol transport pathway. Apo A-IV promotes cholesterol efflux from cells, and activates the enzymes lecithin:cholesterol acyltransferase, cholesterol ester transfer protein and lipoprotein lipase [reviewed in (6)]. Furthermore, strong evidence from experiments in rats suggests that apo A-IV plays a role in the control of food intake, i.e., intravenous and cerebrovascular administration of apo A-IV strongly suppresses food intake, whereas the administration of apo A-IV antiserum stimulates feeding [reviewed in (7)]. Also, apo A-IV modulates gastric acid secretion and gastric emptying in rats in a dose-dependent manner (8,9). Interestingly, apo A-IV has also been reported to have an antioxidant effect in inhibiting lipid peroxidation processes (10,11). Taken together, these findings suggest that apo A-IV may represent an antiatherogenic factor.

Indeed, Cohen et al. (12) and Duverger et al. (13) showed that genetically modified mice carrying several copies of the human or mouse apo A-IV gene developed markedly less atherosclerosis than control mice (12,13). It was even demonstrated that atherosclerosis-prone apo E knockout mice had considerable protection against atherosclerotic lesions when overexpressing the human apo A-IV gene either in liver or in the intestinal tract (11,13). Observations from these studies suggest that apo A-IV acts by increasing the potential of HDL to promote cholesterol efflux from cholesterol-loaded cells (12) and/or by exerting antioxidative properties within the arterial wall (11). In humans, a cross-sectional study in two different ethnic populations revealed an inverse association between plasma apo A-IV concentrations and coronary artery disease (14). This finding was confirmed in a Chinese population study (15) as well as in patients with kidney impairment (16).

The apparent atheroprotective effects of apo A-IV have stimulated interest in the factors involved in the modulation of plasma apo A-IV concentrations. It has been shown that apo A-IV synthesis is stimulated by triacylglycerol-containing diets in rats (17). Weinberg and colleagues (18) observed in humans that serum apo A-IV concentrations are significantly correlated with the percentage of total energy consumed as dietary triacylglycerol. This appears to be true, however, only for fatty acids with >14 carbon atoms. Short- and medium-chain fatty acids do not depend on chylomicron assembly in the intestinal cells, and it has been demonstrated that these fatty acids do not promote the expression of apo A-IV (3). To date, knowledge of the effects of the different longer-chain dietary fatty acids on plasma apo A-IV concentrations is limited and inconsistent. In rats, one group reported similar effects of diets rich in saturated fatty acids (SFA) or PUFA (17), whereas another group observed increased synthesis of apo A-IV in response to oleic acid (18:1) or linoleic acid (18:2) compared with stearic acid (18:0) (3). In the human intestinal Caco-2 cell line, oleic acid and docosahexaenoic acid were more potent than linoleic acid and -linolenic acid in increasing the gene expression and secretion of apo A-IV (19).

Taken together, the studies conducted to date have not fully delineated the effect of dietary fatty acids on plasma apo A-IV concentrations. Therefore, we investigated this issue in healthy volunteers who participated in a strictly controlled dietary study. This study was designed initially to investigate the effect of refined olive oil [rich in monounsaturated fatty acids (MUFA)], rapeseed oil {rich in MUFA and -linolenic acid [18:3(n-3)]}, and sunflower oil rich in (n-6) PUFA] on LDL oxidizability (20).

	SUBJECTS AND METHODS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Participants.

Of 700 students living in boarding school-type conditions in a third-level technical college, 115 nonsmoking volunteers were screened for participation. Inclusion criteria were a body mass index < 27 kg/m², serum cholesterol concentrations < 7.76 mmol/L and triacylglycerol concentrations < 3.39 mmol/L. Of the 115 volunteers, 40 were excluded because of diabetes mellitus (n = 1), hyperlipidemia (n = 3), thyroid disease (n = 5), intake of vitamin supplements (n = 2), hyperuricemia (n = 4) and allergy, intolerance or aversion to foodstuffs contained in the study diets (n = 25). Other exclusion criteria were drug or substance abuse and malabsorption syndromes. Of the 75 students who qualified for participation in the study, 69 (35 men, 34 women), aged 18–43 y were chosen for inclusion by drawing lots. Six subjects withdrew during the study because of intercurrent illness and five withdrew because they were unwilling or unable to comply with the dietary regimen. Fifty-eight participants (31 men, 27 women) finished the study. The complete set of samples for plasma apo A-IV measurement was available for 48 participants (23 men, 25 women). The baseline characteristics of the participants are shown in Table 1. Nineteen women who were taking oral contraceptives were instructed not to stop taking them and not to change to another brand. The participants were also asked not to change their regular lifestyles and their usual level of physical activity throughout the study. The protocol and the objectives of the study were explained to the subjects in detail. All gave written consent. The study protocol was approved by the Ethics Committee of the University of Münster.

The study was conducted in a parallel design and consisted of two consecutive dietary periods for each subject. All participants consumed a baseline high fat diet rich in SFA for 2 wk and were then randomly divided into three groups. This was done using tables of random digits, separate for men and women, which were generated by a professional biostatistician. The study personnel and the participants were aware of group affiliations. Each group consumed a high fat diet containing refined olive oil (8 men, 9 women), rapeseed oil (6 men, 7 women) or sunflower oil (9 men, 9 women), as the principal source of fat for 4 wk. These diets were identical in every respect except for the fatty acid composition (Table 2). The dietary treatments were described in more detail previously (20). Venous blood samples were obtained at the beginning of the study (visit 1), after the baseline period (visit 2), after 2 wk (visit 3) and after 4 wk (visit 4) of the study diets. All samples were drawn after an overnight fast of at least 9 h. The plasma was isolated immediately, and frozen at -70°C before analysis.

Laboratory measurements.

Plasma apo A-IV concentrations were determined using an ELISA that employs affinity-purified rabbit anti-human apo A-IV polyclonal antiserum as the capture antibody and the same antibody coupled to horseradish peroxidase as the detection antibody (21,22). Plasma with a known apo A-IV content (standardized with purified apo A-IV after phenylalanine quantification by HPLC) served as a calibration standard. All samples from one subject were analyzed in triplicate within one series resulting in an intra-assay CV of 4.5%. The person who performed the measurements was unaware of the diet group. Apo A-IV phenotype analysis was performed by isoelectric focusing and immunoblotting (23). The molecular basis for the electrophoretic variants, apo A-IV-1 and apo A-IV-2, is a GT substitution in the third base of codon 360, resulting in a glutamine for histidine change in the mature protein (24,25). This substitution results in an increase in the positive charge of the apo A-IV-1 isoprotein by one unit, which can be detected by isoelectric focusing. The frequencies of the allele 1 vary between 0.88 and 0.94 and of allele 2 between 0.06 and 0.12 in the various populations investigated. Some recent studies have suggested that this polymorphism is associated with increased postprandial hypertriglyceridemia, reduced LDL cholesterol response to dietary cholesterol, and increased HDL cholesterol response to changes in total dietary fat content [reviewed in (26)]. Serum lipid concentrations were measured as described earlier (20).

Statistics.

All statistical calculations were performed using the Statistical Package for the Social Sciences (SPSS, version 10.0, SPSS, Chicago, IL) computer program. Apo A-IV concentrations in plasma appeared to be approximately normally distributed, as confirmed by checking normal plots and histograms of the data and by performing Kolmogorov-Smirnov-tests.

Data were analyzed using repeated-measures ANOVA, with the apo A-IV data of visits 2, 3 and 4 as the three levels of the within-subject factor (time), and apo A-IV genotype, gender, and diet group as between-subject factors. Post-hoc comparisons of visit 2 vs. 3 and 3 vs. 4, respectively, were done by paired t tests. Visits 1 and 2 were also compared by paired t test. These tests were two tailed, and the level of significance for all tests was P < 0.05.

	RESULTS

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 
Apo A-IV concentrations decreased during the baseline diet period (visit 1 to visit 2) by 14% or 13.6 mg/L [95% CI, -6.9 to -20.2 mg/L, T₍₄₇₎ = 4.111, P < 0.001, Table 3]. The three diets rich in unsaturated fatty acids (visits 2–4), however, had the opposite effect. Repeated-measures ANOVA revealed a strong increase in apo A-IV [+13.0 mg/L, F_(2,76) = 12.874, P < 0.001] in the whole group. Although at first sight this increase appeared to be greater in subjects fed the rapeseed oil and sunflower oil diets than in those fed the olive oil diet, there was no effect of diet group affiliation [F_(4,76) = 1.749, P = 0.148 for time x oil group interaction]. Gender and apo A-IV genotype also did not affect the diet-induced increase in plasma apo A-IV levels [F_(2,76) = 0.883, P = 0.418 for time x gender interaction; F_(2,76) = 0.647, P = 0.527 for time x apo A-IV genotype interaction]. Interestingly, the increase in apo A-IV in subjects consuming the three oil diets was not linear [quadratic within-subject contrast for the time effect: F_(1,38) = 19.313, P < 0.001] because apo A-IV concentrations in plasma further decreased in the first 2 wk of diet consumption [visit 2 vs. visit 3: -5.2 mg/L (-6%), 95% CI, -0.5 to -9.9 mg/L, T₍₄₇₎ = 2.210, P = 0.032]. Thus, the increase in plasma apo A-IV concentrations in subjects consuming the three diets rich in unsaturated oils was confined to the last 2 wk of this phase [visit 3 vs. visit 4: +18.2 mg/L (+23%), 95% CI, +12.1 to + 24.2 mg/L, T₍₄₇₎ = 6.055, P < 0.001].

	DISCUSSION

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

Thus, the effect of the dietary fat composition on plasma apo A-IV concentrations differs considerably from the effect of dietary fatty acids on apo A-I concentrations. Unsaturated fatty acids, particularly PUFA, reduce plasma apo A-I concentrations compared with SFA (27), which was also the case in our study (data not shown). Thus, apo A-IV and apo A-I appear to be differently and independently regulated by dietary fat composition. Because both proteins contribute to the reverse cholesterol transport pathway, the increase in plasma apo A-IV concentrations might compensate in part for the decrease in apo A-I concentrations in subjects consuming these diets. An estimation of the effect of these changes on reverse cholesterol transport or on atherosclerosis risk, however, is rather complicated, particularly because the magnitude of the net cholesterol transport to the liver appears to be determined by cellular processes rather than by plasma concentrations of HDL cholesterol or apolipoproteins (28). On the other hand, the observations that transgenic mice overexpressing mouse or human apo A-IV develop distinctly less atherosclerosis (12,13) suggest that the diet-induced increase observed in plasma apo A-IV concentrations might ameliorate the risk of atherosclerosis.

Which factors might have led to the decrease in apo A-IV concentrations when the baseline diet was consumed? The major differences between the habitual diet of the participants and the baseline diet were that the latter offered a lower cholesterol intake, a higher fiber intake and a smaller amount of mono- and disaccharides. The higher fiber intake, in particular, might explain the decrease in apo A-IV concentrations because fiber can slow down and even suppress fat absorption (29). Furthermore, dietary fiber interacts with bile components in the intestinal tract (30), which might also affect apo A-IV synthesis. In addition, the decrease in apo A-IV concentrations in plasma might be due to the reduced cholesterol intake during this phase. A decreased cholesterol consumption is likely to reduce the rate of chylomicron assembly in the intestinal cells, which in turn could slow down apo A-IV synthesis and secretion (3). Consistent with this hypothesis, it was recently reported that apo A-IV concentrations in plasma and in triacylglycerol-rich lipoproteins decreased with consumption of a diet that contained very little cholesterol (31).

The most obvious explanation for the increase in plasma apo A-IV concentrations with consumption of these diets is that the unsaturated fatty acids might have exerted direct effects on the expression and/or secretion of apo A-IV in the intestinal cells. This agrees with findings in the human intestinal Caco-2 cell line, in which isolated fatty acids (oleic, linoleic, -linolenic and docosahexaenoic acids) increased the synthesis of apo A-IV by switching on its gene (19). The effect of SFA was not evaluated in these experiments. Another possible explanation might be an influence of unsaturated fatty acids on apo A-IV catabolism, i.e., its hepatic clearance rate. This would also provide an explanation for the time lag effect seen in subjects consuming these diets because metabolic changes are likely to require far more time to affect plasma concentrations than direct effects on gene expression. However, because we have not investigated these mechanisms, these hypotheses are tentative.

The major limitation of our study is that apo A-IV concentrations were measured ex post. Thus, the number of subjects may have been inadequate for detecting a difference among the diet groups. Also, the study was not explicitly designed to compare the three oil diets with the SFA diet. To this end it would have been sensible to include a fourth group that consumed a SFA diet over the entire period of time. Therefore, hidden time effects, which might have led to the increase in plasma apo A-IV within the last 2 wk of the study, cannot be ruled out completely.

In conclusion, diets rich in unsaturated fatty acids increase plasma concentrations of apo A-IV compared with a baseline diet rich in SFA in healthy men and women. It remains to be established, however, whether such an increase in plasma apo A-IV concentrations lowers the risk of coronary heart disease. Also, our observation of a decrease in plasma apo A-IV concentrations during the baseline diet period suggests that a high fiber intake and/or a low cholesterol intake lowers plasma concentrations of apo A-IV.

	ACKNOWLEDGMENTS

 
We are indebted to B. Jacobs, B. Berning, J. Harmsen, and particularly E. Gramenz for excellent technical assistance; to R. Schmidt, R. Junker, and G. Berger for performing the venipunctures; to the Bildungszentrum der Bundesfinanzverwaltung for generous cooperation; to E. Ostermann and the Camphill Werkstätten, Steinfurt, Germany, for supplying the oil-enriched bread and cake; to the Homann Company, Dissen, Germany, for supplying the specially manufactured margarine; and last but not least to the study subjects for participation.

	FOOTNOTES

 
¹ Supported by grants from the Central Marketing Agency of the German Agricultural Industry (CMA), the German Union for the Promotion of Oil- and Protein Plants (UFOP), and the Brökelmann Ölmühle Company, Hamm, Germany, to M.K. and U.W., and a grant from the Austrian Science Fund (P14717-GEN) to F.K.

³ Abbreviations used: apo, apolipoprotein; MUFA, monounsaturated fatty acids; SFA, saturated fatty acids.

Manuscript received 17 December 2002. Initial review completed 6 February 2003. Revision accepted 11 March 2003.

	LITERATURE CITED

TOP ABSTRACT SUBJECTS AND METHODS RESULTS DISCUSSION LITERATURE CITED

 

1. Weisgraber, K. H., Bersot, T. P. & Mahley, R. W. (1978) Isolation and characterization of an apoprotein from the d less than 1.006 lipoproteins of human and canine lymph homologous with the rat A-IV apoprotein. Biochem. Biophys. Res. Commun. 85:287-292.[Medline]

2. Utermann, G. & Beisiegel, U. (1979) Apolipoprotein A-IV: a protein occurring in human mesenteric lymph chylomicrons and free in plasma. Isolation and quantification. Eur. J. Biochem. 99:333-343.[Medline]

3. Kalogeris, T. J., Monroe, F., Demichele, S. J. & Tso, P. (1996) Intestinal synthesis and lymphatic secretion of apolipoprotein A-IV vary with chain length of intestinally infused fatty acids in rats. J. Nutr. 126:2720-2729.

4. Duverger, N., Ghalim, N., Ailhaud, G., Steinmetz, A., Fruchart, J. C. & Castro, G. (1993) Characterization of apoA-IV-containing lipoprotein particles isolated from human plasma and interstitial fluid. Arterioscler. Thromb. 13:126-132.[Abstract/Free Full Text]

5. Von Eckardstein, A., Huang, Y., Wu, S., Sarmadi, A. S., Schwarz, S., Steinmetz, A. & Assmann, G. (1995) Lipoproteins containing apolipoprotein A-IV but not apolipoprotein A-I take up and esterify cell-derived cholesterol in plasma. Arterioscler. Thromb. Vasc. Biol. 15:1755-1763.[Abstract/Free Full Text]

6. Kalogeris, T. J., Rodriguez, M. D. & Tso, P. (1997) Control of synthesis and secretion of intestinal apolipoprotein A-IV by lipid. J. Nutr. 127:537S-543S.

7. Tso, P., Liu, M., Kalogeris, T. J. & Thomson, A. B. (2001) The role of apolipoprotein A-IV in the regulation of food intake. Annu. Rev. Nutr. 21:231-254.[Medline]

8. Okumura, T., Fukagawa, K., Tso, P., Taylor, I. L. & Pappas, T. N. (1994) Intracisternal injection of apolipoprotein A-IV inhibits gastric secretion in pylorus-ligated conscious rats. Gastroenterology 107:1861-1864.[Medline]

9. Okumura, T., Fukagawa, K., Tso, P., Taylor, I. L., Pappas, T. N., Uehara, A. & Kohgo, Y. (1995) Delayed gastric emptying by central apolipoprotein A-IV in rats. Gastroenterology 108:A996(abs.).

10. Qin, X., Swertfeger, D. K., Zheng, S., Hui, D. Y. & Tso, P. (1998) Apolipoprotein AIV: a potent endogenous inhibitor of lipid oxidation. Am. J. Physiol. 274:H1836-H1840.

11. Ostos, M. A., Conconi, M., Vergnes, L., Baroukh, N., Ribalta, J., Girona, J., Caillaud, J. M., Ochoa, A. & Zakin, M. M. (2001) Antioxidative and antiatherosclerotic effects of human apolipoprotein A-IV in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 21:1023-1028.[Abstract/Free Full Text]

12. Cohen, R. D., Castellani, L. W., Qiao, J. H., Van Lenten, B. J., Lusis, A. J. & Reue, K. (1997) Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV. J. Clin. Investig. 99:1906-1916.[Medline]

13. Duverger, N., Tremp, G., Caillaud, J. M., Emmanuel, F., Castro, G., Fruchart, J. C., Steinmetz, A. & Denefle, P. (1996) Protection against atherogenesis in mice mediated by human apolipoprotein A-IV. Science (Washington, DC) 273:966-968.[Abstract]

14. Kronenberg, F., Stuhlinger, M., Trenkwalder, E., Geethanjali, F. S., Pachinger, O., von Eckardstein, A. & Dieplinger, H. (2000) Low apolipoprotein A-IV plasma concentrations in men with coronary artery disease. J. Am. Coll. Cardiol. 36:751-757.[Abstract/Free Full Text]

15. Warner, M. M., Guo, J. & Zhao, Y. (2001) The relationship between plasma apolipoprotein A-IV levels and coronary heart disease. Chin. Med. J. (Engl. Ed.) 114:275-279.[Medline]

16. Kronenberg, F., Kuen, E., Ritz, E., Konig, P., Kraatz, G., Lhotta, K., Mann, J. F., Muller, G. A., Neyer, U., Riegel, W., Riegler, P., Schwenger, V. & von Eckardstein, A. (2002) Apolipoprotein A-IV serum concentrations are elevated in patients with mild and moderate renal failure. J. Am. Soc. Nephrol. 13:461-469.[Abstract/Free Full Text]

17. Apfelbaum, T. F., Davidson, N. O. & Glickman, R. M. (1987) Apolipoprotein A-IV synthesis in rat intestine: regulation by dietary triglyceride. Am. J. Physiol 252:G662-G666.

18. Weinberg, R. B., Dantzker, C. & Patton, C. S. (1990) Sensitivity of serum apolipoprotein A-IV levels to changes in dietary fat content. Gastroenterology 98:17-24.[Medline]

19. Stan, S., Delvin, E. E., Seidman, E., Rouleau, T., Steinmetz, A., Bendayan, M., Yotov, W. & Levy, E. (1999) Modulation of apo A-IV transcript levels and synthesis by n-3, n-6, and n-9 fatty acids in CACO-2 cells. J. Cell Biochem. 75:73-81.[Medline]

20. Kratz, M., Cullen, P., Kannenberg, F., Kassner, A., Fobker, M., Abuja, P. M., Assmann, G. & Wahrburg, U. (2002) Effects of dietary fatty acids on the composition and oxidizability of low-density lipoprotein. Eur. J. Clin. Nutr. 56:72-81.[Medline]

21. Rosseneu, M., Michiels, G., de Keersgieter, W., Bury, J., De Slypere, J. P., Dieplinger, H. & Utermann, G. (1988) Quantification of human apolipoprotein A-IV by "sandwich"-type enzyme-linked immunosorbent assay. Clin. Chem. 34:739-743.[Abstract/Free Full Text]

22. Kronenberg, F., Lobentanz, E. M., Konig, P., Utermann, G. & Dieplinger, H. (1994) Effect of sample storage on the measurement of lipoprotein[a], apolipoproteins B and A-IV, total and high density lipoprotein cholesterol and triglycerides. J. Lipid Res. 35:1318-1328.[Abstract]

23. De Knijff, P., Rosseneu, M., Beisiegel, U., de Keersgieter, W., Frants, R. R. & Havekes, L. M. (1988) Apolipoprotein A-IV polymorphism and its effect on plasma lipid and apolipoprotein concentrations. J. Lipid Res. 29:1621-1627.[Abstract]

24. Lohse, P., Kindt, M. R., Rader, D. J. & Brewer, H. B., Jr. (1990) Genetic polymorphism of human plasma apolipoprotein A-IV is due to nucleotide substitutions in the apolipoprotein A-IV gene. J. Biol. Chem. 265:10061-10064.[Abstract/Free Full Text]

25. Tenkanen, H., Lukka, M., Jauhiainen, M., Metso, J., Baumann, M., Peltonen, L. & Ehnholm, C. (1991) The mutation causing the common apolipoprotein A-IV polymorphism is a glutamine to histidine substitution of amino acid 360. Arterioscler. Thromb. 11:851-856.[Abstract/Free Full Text]

26. Weinberg, R. B. (2002) Apolipoprotein A-IV polymorphisms and diet-gene interactions. Curr. Opin. Lipidol. 13:125-134.[Medline]

27. Shepherd, J., Packard, C. J., Patsch, J. R., Gotto, A. M., Jr. & Taunton, O. D. (1978) Effects of dietary polyunsaturated and saturated fat on the properties of high density lipoproteins and the metabolism of apolipoprotein A-I. J. Clin. Investig. 61:1582-1592.

28. Jolley, C. D., Woollett, L. A., Turley, S. D. & Dietschy, J. M. (1998) Centripetal cholesterol flux to the liver is dictated by events in the peripheral organs and not by the plasma high density lipoprotein or apolipoprotein A-I concentration. J. Lipid Res. 39:2143-2149.[Abstract/Free Full Text]

29. Munakata, A., Iwane, S., Todate, M., Nakaji, S. & Sugawara, K. (1995) Effects of dietary fiber on gastrointestinal transit time, fecal properties and fat absorption in rats. Tohoku J. Exp. Med. 176:227-238.[Medline]

30. Story, J. A., Furumoto, E. J. & Buhman, K. K. (1997) Dietary fiber and bile acid metabolism—an update. Adv. Exp. Med. Biol. 427:259-266.[Medline]

31. Sun, Z., Welty, F. K., Dolnikowski, G. G., Lichtenstein, A. H. & Schaefer, E. J. (2001) Effects of a National Cholesterol Education Program Step II Diet on apolipoprotein A-IV metabolism within triacylglycerol-rich lipoproteins and plasma. Am. J. Clin. Nutr. 74:308-314.[Abstract/Free Full Text]

This article has been cited by other articles:

				E Wendland, A Farmer, P Glasziou, and A Neil Effect of {alpha} linolenic acid on cardiovascular risk markers: a systematic review Heart, February 1, 2006; 92(2): 166 - 169. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kratz, M. Articles by Kronenberg, F. Search for Related Content PubMed PubMed Citation Articles by Kratz, M. Articles by Kronenberg, F.