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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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Related in: MedlinePlus

Gene expression in colon. qRT-PCR was used to determine normalized gene expression levels in colon of individual wildtype mice that received the control diet (n = 12, 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 and fold changes in parenthesis shown are a Acaa1 (1.29), b Cpt1a (1.37), c Sqle (1.08). All changes are non-significant (p > 0.2, Student's t-test). AU, arbitrary units.
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Figure 2: Gene expression in colon. qRT-PCR was used to determine normalized gene expression levels in colon of individual wildtype mice that received the control diet (n = 12, 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 and fold changes in parenthesis shown are a Acaa1 (1.29), b Cpt1a (1.37), c Sqle (1.08). All changes are non-significant (p > 0.2, Student's t-test). AU, arbitrary units.

Mentions: The genes Acaa1a, Cpt1a, and Sqle, representing three pathways differentially regulated in small intestine, were analyzed by qRT-PCR in individual colon samples (n = 10). In none of the cases a significant difference in gene expression was observed (Figure 2). Exclusion of the two animals from the control group which showed lowest expression for these three genes (10-fold or more) did not influence the outcome of this analysis (maximum FC < 1.15, all non-significant; data not shown). This underscores the different function of the small intestine (mainly uptake and transfer of nutrients) and the colon (mainly water absorption).


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 colon. qRT-PCR was used to determine normalized gene expression levels in colon of individual wildtype mice that received the control diet (n = 12, 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 and fold changes in parenthesis shown are a Acaa1 (1.29), b Cpt1a (1.37), c Sqle (1.08). All changes are non-significant (p > 0.2, Student's t-test). AU, arbitrary units.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Gene expression in colon. qRT-PCR was used to determine normalized gene expression levels in colon of individual wildtype mice that received the control diet (n = 12, 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 and fold changes in parenthesis shown are a Acaa1 (1.29), b Cpt1a (1.37), c Sqle (1.08). All changes are non-significant (p > 0.2, Student's t-test). AU, arbitrary units.
Mentions: The genes Acaa1a, Cpt1a, and Sqle, representing three pathways differentially regulated in small intestine, were analyzed by qRT-PCR in individual colon samples (n = 10). In none of the cases a significant difference in gene expression was observed (Figure 2). Exclusion of the two animals from the control group which showed lowest expression for these three genes (10-fold or more) did not influence the outcome of this analysis (maximum FC < 1.15, all non-significant; data not shown). This underscores the different function of the small intestine (mainly uptake and transfer of nutrients) and the colon (mainly water absorption).

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