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FJ
EXPRESS SUMMARY ARTICLE The Full-length version of this article is also available, published online February 20, 2004 as doi:10.1096/fj.03-0950fje. |
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* UPRES Lipides et Nutrition EA 2422, IFR 92 Qualité des Aliments, Université de Bourgogne, Dijon, France;
Physiologie de la Nutrition, ENSBANA FRE2328 CNRS-CESG/Université de Bourgogne, Dijon, France;
Wageningen University, Wageningen, The Netherlands; and
Unité mixte de recherche INRA-ENSA de Génétique Animale, Rennes, France
3Correspondence: NARCE, UPRES Lipides et Nutrition, Faculté des Sciences Gabriel, Université de Bourgogne, 6 Boulevard Gabriel, 21000 Dijon, France. E-mail: Michel.Narce{at}u-bourgogne.fr
SPECIFIC AIMS
We have noted that the lipogenesis end-product (oleic acid, 18:1n-9, OA) accumulated in spontaneously hypertensive rats (SHR) liver concomitant to the pathogenesis of hypertension and that a dietary combination of n-6/n-3 polyunsaturated fatty acids (PUFA) composed of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and 
-linolenic acid (GLA), (EPA/DHA/GLA) had hypotensive effects. As lipogenesis can be regulated by PUFA, the aim of this investigation was to evaluate possible effects of this hypotensive dietary mixture on the 18:1n-9/18:0 ratio in SHR liver and on the expression of stearoyl CoA desaturase-1 (SCD-1), a key enzyme of OA production.
PRINCIPAL FINDINGS
1. Compared with WKY, most plasma triacylglycerol (TAG) fatty acids were altered in SHR.
The amounts of saturated fatty acids decreased by 
30% when 18:1n-7+n-9 increased by 66%. In SHR, the EPA/DHA/GLA diet increased significantly the amount of saturated fatty acids (16:0 and 18:0, +44% and +118%, respectively), which converge to the level observed in WKY. 18:1n-7+n-9 was significantly decreased by the experimental diet (–17%) but remained significantly higher than in WKY.
In SHR plasma cholesterol esters, the EPA/DHA/GLA diet increased significantly the total amount of saturated and monounsaturated fatty acids, reflecting an increase of 16:0 (+44%) and 18:0 (+118%), 16:1n-7 (+47%), and oleic acid (+22%), respectively. Consequently, levels of saturated and monounsaturated fatty acids observed in EPA/DHA/GLA SHR tended to be similar to those of WKY.
2. In total lipids (TL), phospholipids (PL), and TAG in hepatocytes isolated from treated SHR vs. controls, the relative amount of 18:0 decreased significantly in PL (–16%) and the amount of 18:1n-7+n-9 decreased in TL, PL, and TAG (–14%, –13% and –20%, respectively).
The index of 
9 desaturation, calculated from the ratio 18:1n-7+n-9/18:0, decreased in TL and TAG fractions of the EPA/DHA/GLA group vs. SHR (–16% and –20%, respectively). The hepatocyte fatty acid composition from WKY rats (presented previously) followed the pattern seen in the plasma.
3. Expression of SCD-1 was suppressed by 50% in the EPA/DHA/GLA group vs. the control SHR group, the value remaining higher than in WKY (Fig. 1
).
Nevertheless, after feeding the EPA/DHA/GLA diet, FAS transcript levels remained unchanged. Relating to the nuclear factor SREBP-1, no modulation was observed under the influence of the EPA/DHA/GLA treatment. 18S mRNA levels, used as a loading control, were not changed by the experimental regimen.
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CONCLUSIONS AND SIGNIFICANCE
The present work shows that in addition to reducing blood pressure, treatment of SHR with EPA/DHA/GLA decreased relative amounts of monounsaturated fatty acids in plasma and hepatocyte lipid fractions and decreased the delta-9 desaturation index, usually considered to reflect delta-9 desaturase activity (Table 1
). These changes appeared to be due to a suppression of SCD-1 gene expression and led to a convergence of the relative amounts of monounsaturated fatty acid and of the 18:1n-7+n-9/18:0 ratio to levels similar to those of WKY (Fig. 2
). Therefore, such a PUFA hypotensive diet efficiently reduces lipid disorders linked to spontaneous hypertension. PUFA amounts tended to converge to those of WKY, increasing the amounts in vasodilator prostaglandin precursors. Suppression of 50% of hepatocyte SCD-1 transcripts in EPA/DHA/GLA fed rats indicates a regulation of the enzyme at a transcriptional level. This is the first time that SCD-1 has been shown to be regulated in such pathophysiological conditions by a dietary n-3/n-6 combination. However, FAS and SREBP-1 remained unchanged, showing that the molecular basis for dietary regulation of hepatic genes of lipid metabolism could be different. The research of other nuclear factor candidates for SCD-1 regulation is the subject of ongoing studies. If such a dietary combination is relevant to laboratory studies involving experimental models of hypertension, how relevant these observations are to humans remains to be determined.
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FOOTNOTES
1 To read the full text of this article, go to http://www.fasebj.org/cgi/doi/10.1096/fj.03-0950fje; doi: 10.1096/fj.03-0950fje 
2 J. B. and S.B. contributed equally to this work and should both be considered as first authors.
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