Project description:The aim of this study was to determine the effects of unprotected dietary unsaturated fatty acids (UFA) from different plant oils on gene expression in the mammary gland of grazing dairy cows. Milk composition and gene expression in the mammary gland tissue were evaluated in grazing dairy cows supplemented with different unsaturated fatty acids (UFA). The UFA supplementation improves the health and nutrition quality aspects of dairy milk, but also affects the gene networks expression signature associated with cellular growth and proliferation, cell-death, signalling, nutrient metabolism, and immune response, and in turn, the mammary gland integrity and health. SUBMITTER_CITATION: Mach, N., A. A. A. Jacobs, L. Kruijt, J. Van Baal, and M. A. Smits. 2011. Alteration of gene expression in mammary gland tissue of dairy cows in response to dietary unsaturated fatty acids. Animal.DOI:10.1017/S1751731111000103
Project description:The aim of this study was to determine the effects of unprotected dietary unsaturated fatty acids (UFA) from different plant oils on gene expression in the mammary gland of grazing dairy cows. Milk composition and gene expression in the mammary gland tissue were evaluated in grazing dairy cows supplemented with different unsaturated fatty acids (UFA). The UFA supplementation improves the health and nutrition quality aspects of dairy milk, but also affects the gene networks expression signature associated with cellular growth and proliferation, cell-death, signalling, nutrient metabolism, and immune response, and in turn, the mammary gland integrity and health. A total of 28 Holstein-Friesian dairy cows in mid-lactation were blocked according to parity (2.4 ± 0.63 years), days in milk (DIM; 153 ± 32.8 days), milk yield (25.7 ± 3.08 kg/d) and fat content (4.3 ± 0.12%). Cows were then randomly assigned to four UFA-sources based on rapeseed, soybean, linseed or a mixture of the three oils for 23 days (Period I) after which, all 28 cows were switched to a control diet for an additional 28 days (Period II). On the last day of both periods, mammary gland biopsies were taken to study genome-wide differences in lipid metabolism gene expression.
Project description:Scope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
Project description:Scope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
Project description:Scope: Consumption of industrial trans fatty acids unfavourably alters plasma cholesterol and has been linked to NAFLD. However, the mechanisms underlying these deleterious effects of trans fatty acids are unclear. Here, we aim to investigate the molecular mechanisms of action of industrial trans fatty acids. Methods & Results: Hepa1-6 hepatoma cells were incubated with elaidate, oleate, or palmitate. C57Bl/6 mice were fed diets rich in trans-unsaturated, cis-unsaturated or saturated fatty acids. Transcriptomics analysis of Hepa1-6 cells showed that elaidate but not oleate or palmitate induced expression of genes involved in cholesterol biosynthesis. Induction of cholesterogenesis by elaidate was mediated by increased SREBP2 and dependent on SCAP, yet independent of LXR and UBXD8. Elaidate decreased intracellular free cholesterol levels and repressed the anti-cholesterogenic effect of exogenous cholesterol. In mice, the trans-unsaturated diet increased the ratio of liver to gonadal fat mass, steatosis, hepatic cholesterol levels, ALT activity, and fibrosis markers, suggesting enhanced NAFLD, compared to the cis-unsaturated and saturated diets. Conclusion: Elaidate induces cholesterogenesis in vitro via activation of the SCAP-SREBP axis, likely by lowering intracellular free cholesterol and attenuating cholesterol-dependent repression of SCAP. This pathway potentially underlies the increase in liver cholesterol and NAFLD by industrial trans fatty acids.
Project description:The aim of the present study was to correlate lipid metabolism genes in the mammary gland tissue affected by stage of lactation and nutrition to the resulting milk fatty acids composition in grazing dairy cows, and to classify milk fatty acid (FA) groups based on variations in lipid metabolism gene expression patterns. Identifying the relationship between lipid metabolism genes in the mammary gland tissue and the resulting milk fatty acid composition is expected to greatly contribute to our understanding of milk fatty acid metabolism and to enhance opportunities to improve milk fat composition through nutrition. In fact, SNCA, SCD5, and PNPLA2 lipid metabolism-related genes affected by unsaturated fatty acids supplementation, were found to strongly correlated to different milk FA groups, but also contributed most to the classification of these FA groups, suggesting a significant role in mediating the lipid metabolism in the mammary gland tissue and determining the milk fatty acids composition.
Project description:The aim of the present study was to correlate lipid metabolism genes in the mammary gland tissue affected by stage of lactation and nutrition to the resulting milk fatty acids composition in grazing dairy cows, and to classify milk fatty acid (FA) groups based on variations in lipid metabolism gene expression patterns. Identifying the relationship between lipid metabolism genes in the mammary gland tissue and the resulting milk fatty acid composition is expected to greatly contribute to our understanding of milk fatty acid metabolism and to enhance opportunities to improve milk fat composition through nutrition. In fact, SNCA, SCD5, and PNPLA2 lipid metabolism-related genes affected by unsaturated fatty acids supplementation, were found to strongly correlated to different milk FA groups, but also contributed most to the classification of these FA groups, suggesting a significant role in mediating the lipid metabolism in the mammary gland tissue and determining the milk fatty acids composition. A total of 28 Holstein-Friesian dairy cows in mid-lactation were blocked according to parity (2.4 ± 0.63 years), days in milk (DIM; 153 ± 32.8 days), milk yield (25.7 ± 3.08 kg/d) and fat content (4.3 ± 0.12%). Cows were then randomly assigned to four UFA-sources based on rapeseed, soybean, linseed or a mixture of the three oils for 23 days (Period I) after which, all 28 cows were switched to a control diet for an additional 28 days (Period II). On the last day of both periods, mammary gland biopsies were taken to study genome-wide differences in lipid metabolism gene expression.
Project description:Early embryonic development is enhanced in Holstein cows fed diets enriched in specific polyunsaturated fatty acids. However, the molecular mechanisms affected by specific polyunsaturated fatty acids during early embryonic development in cattle are poorly understood. Therefore, our objective was to evaluate the maternal effects of diets enriched in linoleic or α-linolenic acid on transcriptome profiling of in vivo bovine pre-implantation embryos.
Project description:Background: This study examines the impact of dietary fatty acids on regulation of gene expression in the mammary epithelial cells before and during puberty. Methods: The diets primarily consisted of n-9 monounsaturated fatty acids (olive oil), n-6 polyunsaturated fatty acids (safflower), saturated acids (butter), and the reference AIN-93G diet (soy oil). The dietary regimen mimics the repetitive nature of fatty acid exposure in Western diets. Dietary-induced changes in gene expression were examined in the LCM (Laser Capture Microdissected) captured mammary ductal epithelial cells at day of weaning (21 days) and at the end of puberty (50 days after birth). PCNA immunohistochemistry analysis was used to compare proliferation rates between diets. Results: Genes differentially expressed between each of the test diets and the reference diet in both age groups were significantly enriched by cell cycle genes. Some of these genes were involved in the activation of the cell cycle pathway or the G2/M check point pathway. Although there were some differences in the level of differential expression, all diets showed qualitatively same pattern of differential expression compared to the reference diet. Cluster analysis identified an expanded set of cell cycle as well as immunity and sterol metabolism related clusters of differentially expressed genes. Conclusion: Fatty acid-enriched diets significantly up-regulated proliferation above the normal physiological level at day 50. The higher cellular proliferation during puberty caused by enriched fatty acid diets pose a potential increase risk of mammary cancer in later life. The human homologs of 27 of 62 cell cycle cluster of rat genes are included in a human breast cancer cluster of 45 cell cycle related genes further emphasizing the importance of our findings in the rat model.
Project description:Animal nutrition considerably affects milk composition that influences its nutritional quality. Milk component synthesis and secretion by the mammary gland involve the expression of a large number of genes whose nutritional regulation remains poorly defined. In this study, 16 lactating goats received 4 experimental diets differing in either forage to concentrate ratio (high forage, HF, or low forage, LF) supplemented, or not, with lipids (whole rapeseeds, RS, or sunflower oil, SO) in a 4 x 4 Latin Square design. To investigate the pathways regulated by nutrition, we examined the effect of these diets on the expression of approximately 8400 genes in caprine mammary gland using a bovine oligonucleotide microarray.