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© 2007 American Society for Nutrition J. Nutr. 137:2425-2430, November 2007

Nutrient Requirements and Optimal Nutrition

Diet (n-3) Polyunsaturated Fatty Acid Content and Parity Affect Liver and Erythrocyte Phospholipid Fatty Acid Composition in Female Rats1–3,

Beth Levant4,7,*, Marlies K. Ozias4 and Susan E. Carlson5,6,7

Departments of 4 Pharmacology, Toxicology, and Therapeutics, 5 Dietetics and Nutrition, and 6 Pediatrics and 7 The Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160

* To whom correspondence should be addressed. E-mail: blevant{at}kumc.edu.


   ABSTRACT
TOP
 ABSTRACT
Introduction
 Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 
The fatty acid composition of membrane phospholipids affects the physicochemical properties of the membrane and thus influences cell function. In this study, the effects of 1–4 sequential pregnancies on the phospholipid fatty acid compositions of the maternal liver and erythrocytes were determined in female rats fed diets containing {alpha}-linolenic acid (ALA), ALA and preformed docosahexaenoic acid (DHA; ALA+DHA), or minimal ALA (low ALA). Virgin females, fed the diets for commensurate durations, served as a control for reproduction. Liver and erythrocyte total phospholipid compositions were determined at weaning by TLC/GC. In both tissues, significant main effects of diet and reproductive status were detected for many fatty acids, but a significant interaction of diet, reproductive status, and duration of treatment (no. of reproductive cycles or equivalent time period for virgins) was detected only for DHA, 22:6(n-3). Primiparous dams fed the ALA and low ALA diet had decreased liver DHA content of 31% and 74%, respectively, compared with virgin females fed the ALA diet. Liver DHA did not decrease further after additional reproductive cycles. Liver DHA content was unchanged in parous dams fed the ALA+DHA diet, but virgin females fed this diet exhibited a 50% increase in liver DHA after 13 wk of treatment. Changes in erythrocyte DHA were of similar magnitude and time course to those observed in liver, suggesting that this tissue may serve as a marker for liver DHA status.


   Introduction
TOP
 ABSTRACT
 Introduction
Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 
Long-chain (LC)8-PUFA are a major component of the phospholipids that comprise cell membranes. The fatty acid composition of these phospholipids affects the physicochemical properties of the membrane and thus influences conformation and function of membrane-bound proteins, such as receptors, ion channels, and transporters and also influences cell function by serving as precursors for prostaglandins and other signaling molecules and modulating gene expression through the activation of transcription factors (1–3). Biologically important LC-PUFA include docosahexaenoic acid [DHA; 22:6(n-3)], which is synthesized from the essential fatty acid {alpha}-linolenic acid [ALA; 18:3(n-3)] and arachidonic acid [20:4(n-6)], which is derived from linoleic acid [18:2(n-6)].

Diet (n-3) PUFA content affects the fatty acid composition of liver and a variety of other tissues (4,5) and affects hepatic gene and protein expression (6–8). Maternal liver phospholipid fatty acid composition also changes over the course of pregnancy and lactation (9–12). Previously, we have shown that dietary (n-3) PUFA content and maternal parity interact to affect the phospholipid fatty acid composition of the maternal brain (13); however, little is known about how diet and maternal parity interact to affect the phospholipids of peripheral tissues.

Diets consumed by Western societies contain low levels of (n-3) PUFA, particularly relative to (n-6) PUFA, which compete for elongation and desaturation into LC-PUFA (14). In view of our findings in brain and the potential for women to consume suboptimal levels of (n-3) PUFA, particularly LC-PUFA, this study examines the effects of reproductive activity on phospholipid fatty acid composition of the maternal liver and erythrocytes after sequential reproductive cycles under dietary conditions varying in (n-3) PUFA content.


   Materials and Methods
TOP
 ABSTRACT
 Introduction
 Materials and Methods
Results
 Discussion
 LITERATURE CITED
 
    Animals. All experiments were conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals and were approved by the University of Kansas Medical Center Institutional Animal Care and Use Committee.

Long-Evans rats (70–78 d old; Harlan) were housed in a temperature- and humidity-controlled animal facility with a 12-h-dark/-light cycle (on at 0600) and consumed food and water ad libitum. Rats were obtained at least 5 d prior to the commencement of any treatments and were handled regularly.

    Experimental diets. The formulation of the experimental diets and the fatty acid composition of all diets were detailed in a previous publication (15). The ALA diet was prepared by adding pure nonhydrogenated soybean oil (70 g/kg) to Teklad Basal Diet TD00235. This resulted in an ALA concentration of 5.09 g/kg diet and was identical in formulation to Teklad AIN-93G (16). The ALA+DHA diet was formulated with DHASCO (42.57% DHA by weight; Martek Biosciences) substituted on an equal weight basis for soybean oil such that DHA accounted for 0.7% of the total fat in the diet by weight. The low ALA diet was formulated with linoleic sunflower oil (70 g/kg) and contained 0.32 g/kg ALA. Prior to purchase, rats were fed Teklad Global 18% Protein Rodent diet no. 2018S and Teklad Rodent diet (W) no. 8604 for 5–7 d during acclimatization.

    Study design. Individually housed dams were placed on the respective experimental diets at the time of initial mating and consumed that diet for the duration of the study. Litters were culled to 8 pups on postnatal d 1 and weaned on postnatal d 21. For sequential reproductive cycles, dams were remated 8–10 d after weaning. A reproductive cycle is defined as gestation and nursing of 1 litter to weaning. Age-matched, virgin females served as a control for reproduction and were fed the respective diets (n = 4 per time point for the ALA diet and 6–7 per time point for the ALA+DHA and low ALA diets) for 6, 13, 20, or 27 wk, reflecting the time required to complete 1, 2, 3, or 4 reproductive cycles. At the time of weaning of the last litter or at the end of diet treatment for virgins, rats were killed by decapitation. Trunk blood was collected into tubes containing EDTA (1–2 g/L of blood). Erythrocytes were isolated by centrifugation and washed twice. Livers were rapidly removed and frozen on dry ice. Tissues were stored at –70°C until used for analysis of fatty acids.

    Fatty acid analysis. Total phospholipid fatty acid composition was determined as previously described (15). Briefly, lipids were extracted from each sample with chloroform-methanol and fractionated by TLC. The band containing phospholipids was removed and transmethylated with boron trifluoride methanol (Sigma) to yield fatty acid methyl esters. Individual fatty acid methyl esters were separated on a Varian 3400 gas chromatograph with an SP-2330 capillary column (30 m, Supelco) with helium used as the carrier gas. The resulting peaks were identified by comparison to authentic standards (PUFA 1 and 2; Supelco and docosapentaenoic acid [DPA; 22:5(n-6)], Nu-Chek Prep) and expressed as percent of total fatty acids on the basis of peak area.

    Data analysis. Results are presented as the mean ± SEM. Data were analyzed for significant main effects on each fatty acid by 3-way ANOVA with factors of diet (ALA, DHA+ALA, or low ALA), reproductive status (virgin or parous), and duration of treatment (1–4 reproductive cycles or equivalent time period for virgins). Post hoc analysis using ANOVA and Tukey's test (with all groups) was performed only for DHA and (n-6) DPA, where significant interactions of 2 or more factors were observed. After initial analysis indicated no effect of duration of treatment with the ALA diet in virgin females, data for these animals were pooled across the 4 time points and used as a single ALA diet-virgin group in the post hoc analyses. Differences between groups were considered significant at P < 0.05.


   Results
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
Discussion
 LITERATURE CITED
 
Total phospholipid fatty acid composition of liver and erythrocytes were similar to those previously reported (5,17–19) with minor differences likely attributable to differences in strain, sex, and the lipid composition of the diets.

    Effects in liver. Three-way ANOVA with factors of diet, reproductive status, and duration of treatment indicated significant main effects of diet and/or reproductive status for a number of phospholipid fatty acids. A significant main effect of duration of treatment was detected only for (n-6) DPA, which was greater with increasing duration of treatment (Fig. 1B). Accordingly, the effects of diet and reproductive status on hepatic fatty acid composition are presented for groups pooled across treatment durations (Table 1). Low (n-3) content in the diet resulted in decreased levels of 18:2(n-6), 20:5(n-3), 22:5(n-3), and DHA and increased levels of 22:4(n-6) and (n-6) DPA compared with the ALA and ALA+DHA groups regardless of reproductive status. Parous reproductive status resulted in increased 16:0, 18:1(n-9), other monounsaturated fatty acid (MUFA) [16:1, 17:1, and 20:1(n-9) combined], 18:3(n-6), 20:3(n-6), and (n-6) DPA; and decreased 20:2(n-6), 20:4(n-6), and DHA compared with virgin females regardless of diet.


Figure 1
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  		FIGURE 1  Effects of diet (n-3) PUFA content and sequential reproductive cycles on the percentages of DHA (A) and (n-6) DPA (B) contents of rat liver. Data are means ± SEM, n = 16 (ALA diet-virgin) or 6–7 (all other groups). aDifferent from ALA diet-virgin, P < 0.05. bParous different from virgin, same diet, and duration of treatment, P < 0.05. cDifferent from 1 reproductive cycle, same diet, P < 0.05. dDifferent from 2 reproductive cycles, same diet, P < 0.05.

 

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  		TABLE 1 Effects of diet (n-3) PUFA content and reproductive status on liver phospholipid fatty acid composition in female rats1

 
A significant interaction of diet, reproductive status, and duration of treatment was detected only for DHA (Fig. 1A). An interaction of diet and duration of treatment was detected for (n-6) DPA (Fig. 1B). Hepatic DHA content of virgin females fed the ALA+DHA diet increased 50% after 13 wk of treatment, compared with virgin controls, but no further increase occurred with additional duration of treatment. In virgin females fed the low ALA diet, liver DHA content decreased 28% after 6 wk of treatment compared with virgin controls and was not further decreased with longer treatment. Primiparous dams fed the ALA and low ALA diets exhibited decreased percentages of DHA of 31 and 74%, respectively, compared with virgin controls, but no additional decrease was observed in multiparous dams fed these diets. Compensatory incorporation of (n-6) DPA was observed in all instances where DHA content was decreased and roughly paralleled the change in DHA, except in virgin females fed the low ALA diet, where hepatic (n-6) DPA continued to increase over the initial 20 wk of treatment. Parous dams fed the ALA+DHA diet exhibited no change in hepatic DHA or (n-6) DPA levels after as many as 4 sequential reproductive cycles.

    Effects in erythrocytes. Three-way ANOVA with factors of diet, reproductive status, and duration of treatment indicated significant main effects of diet and/or reproductive status for a number of phospholipid fatty acids. A significant main effect of duration of treatment was found only for 18:1(n-7), which increased with treatment duration (not shown). Accordingly, the effects of diet and reproductive status on erythrocyte fatty acid composition are presented for groups pooled across treatment durations (Table 2). Low (n-3) content in the diet resulted in decreased levels of 20:5(n-3), 22:5(n-3), and DHA and increased levels of 22:4(n-6) and (n-6) DPA compared with the ALA and ALA+DHA groups regardless of reproductive status. Parous reproductive status resulted in increased levels, or trends toward an increase, of 16:0, 18:1(n-9), 18:1(n-7), 18:3(n-6), and (n-6) DPA and decreased levels, or trends toward a decrease, of 18:0 and DHA compared with virgin females regardless of diet.


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  		TABLE 2 Effects of diet (n-3) PUFA content and reproductive status on erythrocyte phospholipid fatty acid composition in female rats1

 
A significant interaction of diet, reproductive status, and duration of treatment was detected only for DHA (Fig. 2A). An interaction of diet and reproductive status was detected for (n-6) DPA (Fig. 2B). Virgin females fed the ALA+DHA diet exhibited a gradual increase in erythrocyte DHA levels, which were 45% higher than virgin controls after 27 wk of treatment. Virgin females fed the low ALA diet exhibited decreased erythrocyte DHA content of 55% compared with virgins fed the ALA diet after 6 wk, with no effect of additional treatment duration. Primiparous dams fed the ALA and low ALA diets exhibited decreased percentage of DHA in erythrocytes of 40 and 66% compared with virgin controls, but no further decrease was observed in multiparous dams fed these diets. Compensatory incorporation of (n-6) DPA was detected in all groups where decreased DHA content was observed and was maximal after 1 reproductive cycle or equivalent treatment duration. Parous dams fed the ALA+DHA diet exhibited no change in erythrocyte DHA or (n-6) DPA levels after as many as 4 sequential reproductive cycles.


Figure 2
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  		FIGURE 2  Effects of diet (n-3) PUFA content and sequential reproductive cycles on the percentages of DHA (A) and (n-6) DPA (B) contents of rat erythrocytes. Data are means ± SEM, n = 16 (virgin ALA) or 5–6 (all other groups). aDifferent from ALA diet-virgin, P < 0.05. bParous different from virgin, same diet, and duration of treatment, P < 0.05.

 

   Discussion
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
LITERATURE CITED
 
In agreement with previous studies (4,5), diets varying in (n-3) PUFA content produced changes in phospholipid fatty acid composition of liver and erythrocytes with notable changes in DHA content. Diet- and/or reproduction-induced alterations in a variety of other fatty acids were observed in these tissues; however, these changes were either small in magnitude or occurred in low abundance fatty acids, suggesting that the changes in DHA are of primary importance. In agreement with previous studies, increased or decreased tissue DHA content were accompanied by a compensatory changes in (n-6) DPA (15,20), although the somewhat higher linoleic acid content of the low ALA diet compared with the ALA and ALA+DHA diets may have also contributed to higher tissue levels of (n-6) DPA in tissues of rats fed the low ALA diet. Likewise, the fatty acid composition of these tissues was altered by reproductive activity, with decreased maternal liver and erythrocyte DHA content observed after the weaning of 1 litter, concordant with previous reports (12). Moreover, our findings indicate that diet and reproductive status, as well as duration of treatment (i.e. number of reproductive cycles or equivalent time period for virgins), interact to affect the DHA content of both liver and erythrocytes. Decreased plasma or erythrocyte DHA levels after pregnancy are reported in women (21–23); however, human studies indicate greater depletion in multiparous than in null- or primiparous women (24–26), which differs from the present findings where effects on DHA were maximal after a single reproductive cycle. The mechanism underlying this apparent basement effect for maternal liver and erythrocyte DHA must be determined in future studies.

Interestingly, parous dams fed the ALA-containing diet exhibited significantly decreased liver and erythrocyte DHA levels, although of smaller magnitude than those observed in parous dams fed the low ALA diet. In contrast, liver and erythrocyte DHA levels were unchanged in parous dams fed the diet containing ALA+DHA, which increased the DHA content of these tissues in virgin females. Although the ALA diet used in this study is identical in composition to AIN 93G, which meets all current nutrient standards for reproducing and developing rats (16), our findings suggest that some of the alterations in liver phospholipids observed in previous studies in which rats were fed standard laboratory diets (9,11,12) may be the result of inadequate nutrition, perhaps in concert with the physiological changes associated with pregnancy and lactation, and argues for the inclusion of preformed DHA in diets for reproducing females. The 8- to 10-d interval between weaning and remating used for sequential reproductive cycles in this study may have also contributed to the decreased liver and erythrocyte DHA contents in parous dams fed the ALA-containing diet; however, the alterations in tissue PUFA composition did not differ between primiparous and multiparous dams, suggesting that the recovery period between reproductive cycles was not a major factor in the present observations.

The fatty acid composition of the diet influences membrane phospholipid composition and both influence cellular function. In hepatocytes, variation in availability of (n-3) PUFA altered expression of genes encoding a variety of proteins, including several cytochromes P-450 (27–29). In vivo, dietary PUFA composition influenced hepatic expression of genes encoding many proteins, including those involved in lipid transport and synthesis, lipoprotein metabolism, bile acid metabolism, heme synthesis and utilization, and enzymes including cytochromes P-450 and peroxidases (6,7). Regulation of enzymes involved in the elongation and desaturation of LC-PUFA were affected (8,17). Thus, altered liver PUFA status may contribute to the presumably hormone-dependent alterations in lipid metabolism that occur during pregnancy (30). Furthermore, changes in liver phospholipid composition could potentially contribute to the pathology underlying pregnancy-associated intrahepatic cholestasis or acute steatosis, as well as the hepatic involvement in preeclampsia (30). In addition, with the change in P-450 expression, changes in liver phospholipids could result in altered metabolism of xenobiotics. Similarly, manipulation of erythrocyte membrane PUFA composition altered the activities of several membrane-bound ATPases and acetylcholinesterase and thus may affect the function of these cells as well (19).

Although the changes in overall phospholipid fatty acid composition of liver and erythrocytes as a result of diet and reproductive status were not identical, both tissues exhibited changes in DHA. In fact, the time course and magnitude of changes in these tissues were quite similar, suggesting that assessment of erythrocyte DHA status could represent a proxy measure for monitoring liver DHA status clinically. In contrast, the changes in DHA status of these tissues differ from that observed in brain (13). Whereas the decreased brain phospholipid DHA concentration in the reproducing female was also maximal after a single reproductive cycle consuming a diet lacking ALA, the magnitude of the decrease was smaller than that observed in liver and erythrocytes (~20 vs. 74 and 66%). In addition, the incorporation of (n-6) DPA in brain continued through the 2nd reproductive cycle in dams fed an ALA-deficient diet but was maximal in erythrocytes of primiparous. Moreover, although the DHA contents of liver and erythrocytes decreased in reproducing dams fed the ALA-containing diet, these animals exhibited no decreased brain DHA concentration even after as many as 4 sequential reproductive cycles (13). These observations concur with previous findings that liver and erythrocytes were more vulnerable to DHA depletion than brain (4), which may be a function of differential regulation of DHA synthesis in brain and liver when the diet contains inadequate (n-3) PUFA (17,31).

In conclusion, our findings demonstrate alterations in liver and erythrocyte phospholipid fatty acid composition as a result of dietary (n-3) PUFA content or reproductive status and that these factors interact to affect the DHA statuses of these tissues. The resulting changes in liver DHA status underscore the importance of appropriate nutrition during pregnancy and lactation to maintain optimal hepatic function. The quantitative similarity of the changes in DHA of liver and erythrocytes suggests that erythrocyte DHA levels may serve as a marker for liver DHA status.


   ACKNOWLEDGMENTS
 
We thank Paul F. Davis for technical assistance.


   FOOTNOTES
 
1 Supported by NIH MH071599, Center Grant HD02528, and RR016475 from the INBRE Program of the National Center for Research Resources. Back

2 Author disclosures: B. Levant, M. K. Ozias, and S. E. Carlson, no conflicts of interest. Back

3 Supplemental Tables 1 and 2 are available with the online posting of this paper at jn.nutrition.org. Back

8 Abbreviations used: ALA, {alpha}-linolenic acid; DHA, docosahexaenoic acid; (n-6) DPA, docosapentaenoic acid; LC, long-chain; MUFA, monounsaturated fatty acid. Back

Manuscript received 16 May 2007. Initial review completed 14 June 2007. Revision accepted 13 August 2007.


   LITERATURE CITED
TOP
 ABSTRACT
 Introduction
 Materials and Methods
 Results
 Discussion
 LITERATURE CITED
 

1. Salem N Jr, Litman B, Kim H-Y, Gawrisch K. Mechanisms of action of docosahexaenoic acid in the nervous system. Lipids. 2001;36:945–60.[Medline]

2. Uauy R, Mena P, Rojas C. Essential fatty acids in early life: structural and functional role. Proc Nutr Soc. 2000;59:3–15.[Medline]

3. Horrocks LA, Farooqui AA. Docosahexaenoic acid in the diet: its importance in maintenance and restoration of neural membrane function. Prostaglandins Leukot Essent Fatty Acids. 2004;70:361–72.[Medline]

4. Bourre JM, Dumont OS, Piciotti MJ, Pascal GA, Durand GA. Dietary alpha-linolenic acid deficiency in adult rats for 7 months does not alter brain docosahexaenoic acid content, in contrast to liver, heart and testes. Biochim Biophys Acta. 1992;1124:119–22.[Medline]

5. Salem N Jr, Hullin F, Yoffe AM, Karanian JW, Kim HY. Fatty acid and phospholipid species composition of rat tissues after a fish oil diet. Adv Prostaglandin Thromboxane Leukot Res. 1989;19:618–22.[Medline]

6. Berger A, Roberts MA, Hoff B. How dietary arachidonic- and docosahexaenoic- acid rich oils differentially affect the murine hepatic transcriptome. Lipids Health Dis. 2006;5:10.[Medline]

7. Polozova A, Gionfriddo E, Salem N Jr. Effect of docosahexaenoic acid on tissue targeting and metabolism of plasma lipoproteins. Prostaglandins Leukot Essent Fatty Acids. 2006;75:183–90.[Medline]

8. Igarashi M, Ma K, Chang L, Bell JM, Rapoport SI, DeMar JC Jr. Low liver conversion rate of alpha-linolenic to docosahexaenoic acid in awake rats on a high-docosahexaenoate-containing diet. J Lipid Res. 2006;47:1812–22.[Abstract/Free Full Text]

9. Cunnane SC, Armstrong JK. Long-chain fatty acid composition of maternal liver lipids during pregnancy and lactation in the rat: comparison of triglyceride to phospholipid. J Nutr. 1990;120:338–45.[Abstract/Free Full Text]

10. Innis SM. The activity of 3-hydroxy-3-methylglutaryl-CoA reductase and acyl-CoA: cholesterol acyltransferase in hepatic microsomes from male, female and pregnant rats. The effect of cholestyramine treatment and the relationship of enzyme activity to microsomal lipid composition. Biochim Biophys Acta. 1986;875:355–61.[Medline]

11. Smith RW, Walsh A. Composition of liver lipids of the rat during pregnancy and lactation. Lipids. 1975;10:643–5.[Medline]

12. Dhami MS, de la Iglesia FA, Feuer CF, Feuer G. Phospholipids in the liver of the pregnant rat: changes in fatty acid content and composition. Toxicol Appl Pharmacol. 1979;51:157–66.[Medline]

13. Levant B, Ozias MK, Carlson SE. Diet (n-3) polyunsaturated fatty acid content and parity interact to alter maternal rat brain phospholipid fatty acid composition. J Nutr. 2006;136:2236–42.[Abstract/Free Full Text]

14. Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002;56:365–79.[Medline]

15. Levant B, Ozias MK, Jones KA, Carlson SE. Differential effects of modulation of docosahexaenoic acid content during development in specific regions of rat brain. Lipids. 2006;41:407–14.[Medline]

16. Reeves PG, Nielsen FH, Fahey GC Jr. AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet. J Nutr. 1993;123:1939–51.[Abstract/Free Full Text]

17. Igarashi M, DeMar JC Jr, Ma K, Chang L, Bell JM, Rapoport SI. Upregulated liver conversion of alpha-linolenic acid to docosahexaenoic acid in rats on a 15 week n-3 PUFA-deficient diet. J Lipid Res. 2007;48:152–64.[Abstract/Free Full Text]

18. Okita M, Sasagawa T, Ohta Y, Kaneyuki T, Suzuki K. Effect of arachidonic acid-rich oil on lipids and arachidonate metabolites in ethanol- treated rats. Prostaglandins Leukot Essent Fatty Acids. 2001;64:273–9.[Medline]

19. Vajreswari A, Rupalatha M, Rao PS. Effect of altered dietary n-6-to-n-3 fatty acid ratio on erythrocyte lipid composition and membrane-bound enzymes. J Nutr Sci Vitaminol (Tokyo). 2002;48:365–70.[Medline]

20. Galli C, Trzeciak HI, Paoletti R. Effects of dietary fatty acids on the fatty acid composition of brain ethanolamine phosphoglyceride: reciprocal replacement of n-6 and n-3 polyunsaturated fatty acids. Biochim Biophys Acta. 1971;248:449–54.

21. Al MD, van Houwelingen AC, Kester AD, Hasaart TH, de Jong AE, Hornstra G. Maternal essential fatty acid patterns during normal pregnancy and their relationship to the neonatal essential fatty acid status. Br J Nutr. 1995;74:55–68.[Medline]

22. Holman RT, Johnson SB, Ogburn PL. Deficiency of essential fatty acids and membrane fluidity during pregnancy and lactation. Proc Natl Acad Sci USA. 1991;88:4835–9.[Abstract/Free Full Text]

23. Otto SJ, Houwelingen AC, Antal M, Manninen A, Godfrey K, Lopez-Jaramillo P, Hornstra G. Maternal and neonatal essential fatty acid status in phospholipids: an international comparative study. Eur J Clin Nutr. 1997;51:232–42.[Medline]

24. Hornstra G, Al MD, van Houwelingen AC, Foreman-van Drongelen MMHP. Essential fatty acids in pregnancy and early human development. Eur J Obstet Gynecol Reprod Biol. 1995;61:57–62.[Medline]

25. Al MD, van Houwelingen AC, Hornstra G. Relation between birth order and the maternal and neonatal docosahexaenoic acid status. Eur J Clin Nutr. 1997;51:548–53.[Medline]

26. van den Ham EC, van Houwelingen AC, Hornstra G. Evaluation of the relation between n-3 and n-6 fatty acid status and parity in nonpregnant women from the Netherlands. Am J Clin Nutr. 2001;73:622–7.[Abstract/Free Full Text]

27. Li CC, Lii CK, Liu KL, Yang JJ, Chen HW. n-6 and n-3 polyunsaturated fatty acids down-regulate cytochrome P-450 2B1 gene expression induced by phenobarbital in primary rat hepatocytes. J Nutr Biochem. 2006;17:707–15.[Medline]

28. Sung M, Kim I, Park M, Whang Y, Lee M. Differential effects of dietary fatty acids on the regulation of CYP2E1 and protein kinase C in human hepatoma HepG2 cells. J Med Food. 2004;7:197–203.[Medline]

29. Jump DB, Thelen A, Mater M. Dietary polyunsaturated fatty acids and hepatic gene expression. Lipids. 1999;34 Suppl:S209–12.[Medline]

30. Cunningham G, Leveno K, Bloom S, Hauth J, Gilstrap L III, Wenstrom K, editors. Williams Obstetrics. 22nd ed. New York: McGraw-Hill; 2005.

31. Igarashi M, Demar JC Jr, Ma K, Chang L, Bell JM, Rapoport SI. Docosahexaenoic acid synthesis from {alpha}-linolenic acid by rat brain is unaffected by dietary n-3 PUFA deprivationboxs. J Lipid Res. 2007;48:1150–8.[Abstract/Free Full Text]





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