Abstract
BackgroundDietary 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.ResultsThe 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.ConclusionWe 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.
Highlights
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
Since the most prominent health benefits have been associated with the long-chain n-3 PUFA of marine origin, we have investigated the molecular effects of eicosapentaenoic acid (EPA; 20:5 n-3) and docosahexaenoic acid (DHA; 22:6 n-3) in n-3 high-fat diets
Glucose tolerance tests showed significantly increased glucose tolerance by increasing amounts of EPA&DHA in the diets, correlating with decreased fasting plasma insulin levels. This was associated with induction of mitochondrial biogenesis and beta-oxidation of fatty acids in white adipose tissue (WAT) based on gene and protein expression, but not in the liver [8]
Summary
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. To elucidate molecular effects of n-3 PUFA in vivo, gene expression analyses have been undertaken in animal models using a variety of dietary fatty acids in several tissues, including brain, liver, heart, and adipose [6,7,8,9,10,11,12,13,14,15,16] The majority of those studies focused on liver and white adipose tissue (WAT), which is not surprising given the fact that these are considered the main target organs in a dietary intervention with fatty acids. Recent studies [18,19] showed a clear and significant difference of intestinal gene expression between diets high in diacylglycerol versus triacylglycerol, indicating a profound contribution of the small intestine to fatty acid metabolism. Induction of lipid catabolism genes in the intestine may be involved in the anti-obesity effect of diacylglycerols as compared with triacylglycerols [18,19] and it may even contribute to a differential sensitivity of two inbred mice strains to an obesogenic high-fat diet [20]
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