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Induction of lipid oxidation by polyunsaturated fatty acids of marine origin in small intestine of mice fed a high-fat diet.

van Schothorst EM, Flachs P, Franssen-van Hal NL, Kuda O, Bunschoten A, Molthoff J, Vink C, Hooiveld GJ, Kopecky J, Keijer J - BMC Genomics (2009)

Bottom Line: Dietary polyunsaturated fatty acids (PUFA), in particular the long chain marine fatty acids docosahexaenoic (DHA) and eicosapentaenoic (EPA), are linked to many health benefits in humans and in animal models.Little is known of the molecular response to DHA and EPA of the small intestine, and the potential contribution of this organ to the beneficial effects of these fatty acids.Quantitative real time PCR, and -- in a second animal experiment -- intestinal fatty acid oxidation measurements confirmed significant gene expression differences and showed in a dose-dependent manner significant changes at biological functional level.

View Article: PubMed Central - HTML - PubMed

Affiliation: Food Bioactives Group, RIKILT Institute of Food Safety, Wageningen UR, Wageningen, The Netherlands. evert.vanschothorst@wur.nl

ABSTRACT

Background: Dietary polyunsaturated fatty acids (PUFA), in particular the long chain marine fatty acids docosahexaenoic (DHA) and eicosapentaenoic (EPA), are linked to many health benefits in humans and in animal models. Little is known of the molecular response to DHA and EPA of the small intestine, and the potential contribution of this organ to the beneficial effects of these fatty acids. Here, we assessed gene expression changes induced by DHA and EPA in the wildtype C57BL/6J murine small intestine using whole genome microarrays and functionally characterized the most prominent biological process.

Results: The main biological process affected based on gene expression analysis was lipid metabolism. Fatty acid uptake, peroxisomal and mitochondrial beta-oxidation, and omega-oxidation of fatty acids were all increased. Quantitative real time PCR, and -- in a second animal experiment -- intestinal fatty acid oxidation measurements confirmed significant gene expression differences and showed in a dose-dependent manner significant changes at biological functional level. Furthermore, no major changes in the expression of lipid metabolism genes were observed in the colon.

Conclusion: We show that marine n-3 fatty acids regulate small intestinal gene expression and increase fatty acid oxidation. Since this organ contributes significantly to whole organism energy use, this effect on the small intestine may well contribute to the beneficial physiological effects of marine PUFAs under conditions that will normally lead to development of obesity, insulin resistance and diabetes.

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Gene expression in small intestine. Quantatative real-time PCR (qRT-PCR) was used to determine normalized gene expression levels in small intestine of individual wildtype mice that received the control diet (n = 10, white bars) or EPA&DHA diet (n = 11, black bars). Gene expression levels were normalized using calnexin and averaged per group; the mean expression level of the control group was arbitrarily set at 1. Bars are presented as mean ± standard error. Genes shown (with the mean ratio between the groups shown in parenthesis) are a Acaa1 (2.52), b Acacb (3.91), c Cpt1a (2.79), d Hsd3b (1.91), e Pdk4 (3.24), f Sqle (-1.55). Statistical significance was analyzed using Student's t-test: * p < 0.05, ** p < 0.01. AU, arbitrary units.
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Figure 1: Gene expression in small intestine. Quantatative real-time PCR (qRT-PCR) was used to determine normalized gene expression levels in small intestine of individual wildtype mice that received the control diet (n = 10, white bars) or EPA&DHA diet (n = 11, black bars). Gene expression levels were normalized using calnexin and averaged per group; the mean expression level of the control group was arbitrarily set at 1. Bars are presented as mean ± standard error. Genes shown (with the mean ratio between the groups shown in parenthesis) are a Acaa1 (2.52), b Acacb (3.91), c Cpt1a (2.79), d Hsd3b (1.91), e Pdk4 (3.24), f Sqle (-1.55). Statistical significance was analyzed using Student's t-test: * p < 0.05, ** p < 0.01. AU, arbitrary units.

Mentions: To investigate in more detail inter-individual variation in gene expression and significance of the induced gene expression changes by nutritional treatment, we selected the following 6 genes representing the major pathways being influenced by the diet intervention (see above): fatty acid β-oxidation in peroxisomes (Acaa1a) and mitochondria (Cpt1a and Acacb), the switch between glycolysis and fatty acid oxidation (Pdk4), biosynthesis of steroid hormones (Hsd3b), and biosynthesis of cholesterol (Sqle). For all genes we observed that the mean gene expression ratios (n = 10–11 per dietary group) were similar to the observed ratios by microarray analysis of pooled samples. More importantly, gene expression changes using individual samples were statistically significant for all genes (Figure 1, Table 3).


Induction of lipid oxidation by polyunsaturated fatty acids of marine origin in small intestine of mice fed a high-fat diet.

van Schothorst EM, Flachs P, Franssen-van Hal NL, Kuda O, Bunschoten A, Molthoff J, Vink C, Hooiveld GJ, Kopecky J, Keijer J - BMC Genomics (2009)

Gene expression in small intestine. Quantatative real-time PCR (qRT-PCR) was used to determine normalized gene expression levels in small intestine of individual wildtype mice that received the control diet (n = 10, white bars) or EPA&DHA diet (n = 11, black bars). Gene expression levels were normalized using calnexin and averaged per group; the mean expression level of the control group was arbitrarily set at 1. Bars are presented as mean ± standard error. Genes shown (with the mean ratio between the groups shown in parenthesis) are a Acaa1 (2.52), b Acacb (3.91), c Cpt1a (2.79), d Hsd3b (1.91), e Pdk4 (3.24), f Sqle (-1.55). Statistical significance was analyzed using Student's t-test: * p < 0.05, ** p < 0.01. AU, arbitrary units.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2662879&req=5

Figure 1: Gene expression in small intestine. Quantatative real-time PCR (qRT-PCR) was used to determine normalized gene expression levels in small intestine of individual wildtype mice that received the control diet (n = 10, white bars) or EPA&DHA diet (n = 11, black bars). Gene expression levels were normalized using calnexin and averaged per group; the mean expression level of the control group was arbitrarily set at 1. Bars are presented as mean ± standard error. Genes shown (with the mean ratio between the groups shown in parenthesis) are a Acaa1 (2.52), b Acacb (3.91), c Cpt1a (2.79), d Hsd3b (1.91), e Pdk4 (3.24), f Sqle (-1.55). Statistical significance was analyzed using Student's t-test: * p < 0.05, ** p < 0.01. AU, arbitrary units.
Mentions: To investigate in more detail inter-individual variation in gene expression and significance of the induced gene expression changes by nutritional treatment, we selected the following 6 genes representing the major pathways being influenced by the diet intervention (see above): fatty acid β-oxidation in peroxisomes (Acaa1a) and mitochondria (Cpt1a and Acacb), the switch between glycolysis and fatty acid oxidation (Pdk4), biosynthesis of steroid hormones (Hsd3b), and biosynthesis of cholesterol (Sqle). For all genes we observed that the mean gene expression ratios (n = 10–11 per dietary group) were similar to the observed ratios by microarray analysis of pooled samples. More importantly, gene expression changes using individual samples were statistically significant for all genes (Figure 1, Table 3).

Bottom Line: Dietary polyunsaturated fatty acids (PUFA), in particular the long chain marine fatty acids docosahexaenoic (DHA) and eicosapentaenoic (EPA), are linked to many health benefits in humans and in animal models.Little is known of the molecular response to DHA and EPA of the small intestine, and the potential contribution of this organ to the beneficial effects of these fatty acids.Quantitative real time PCR, and -- in a second animal experiment -- intestinal fatty acid oxidation measurements confirmed significant gene expression differences and showed in a dose-dependent manner significant changes at biological functional level.

View Article: PubMed Central - HTML - PubMed

Affiliation: Food Bioactives Group, RIKILT Institute of Food Safety, Wageningen UR, Wageningen, The Netherlands. evert.vanschothorst@wur.nl

ABSTRACT

Background: Dietary polyunsaturated fatty acids (PUFA), in particular the long chain marine fatty acids docosahexaenoic (DHA) and eicosapentaenoic (EPA), are linked to many health benefits in humans and in animal models. Little is known of the molecular response to DHA and EPA of the small intestine, and the potential contribution of this organ to the beneficial effects of these fatty acids. Here, we assessed gene expression changes induced by DHA and EPA in the wildtype C57BL/6J murine small intestine using whole genome microarrays and functionally characterized the most prominent biological process.

Results: The main biological process affected based on gene expression analysis was lipid metabolism. Fatty acid uptake, peroxisomal and mitochondrial beta-oxidation, and omega-oxidation of fatty acids were all increased. Quantitative real time PCR, and -- in a second animal experiment -- intestinal fatty acid oxidation measurements confirmed significant gene expression differences and showed in a dose-dependent manner significant changes at biological functional level. Furthermore, no major changes in the expression of lipid metabolism genes were observed in the colon.

Conclusion: We show that marine n-3 fatty acids regulate small intestinal gene expression and increase fatty acid oxidation. Since this organ contributes significantly to whole organism energy use, this effect on the small intestine may well contribute to the beneficial physiological effects of marine PUFAs under conditions that will normally lead to development of obesity, insulin resistance and diabetes.

Show MeSH
Related in: MedlinePlus