LDL-Receptor mRNA Expression in Men Is Downregulated within an Hour of an Acute Fat Load and Is Influenced by Genetic Polymorphism
Little is known about the immediate effects of dietary fat on the expression of genes involved in cholesterol metabolism in humans. We investigated the effects of a high-fat meal on circulating mononuclear cell messenger RNA (mRNA) for the LDL receptor (LDLR), LDLR-related protein (LRP), and 3-hydro...
| Main Authors: | , , |
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| Format: | Journal Article |
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American Society for Nutritional Sciences
2007
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| Online Access: | http://jn.nutrition.org/cgi/content/full/137/9/2062 http://hdl.handle.net/20.500.11937/17850 |
| _version_ | 1848749577332588544 |
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| author | Pocathikorn, A. Taylor, R. Mamotte, Cyril |
| author_facet | Pocathikorn, A. Taylor, R. Mamotte, Cyril |
| author_sort | Pocathikorn, A. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Little is known about the immediate effects of dietary fat on the expression of genes involved in cholesterol metabolism in humans. We investigated the effects of a high-fat meal on circulating mononuclear cell messenger RNA (mRNA) for the LDL receptor (LDLR), LDLR-related protein (LRP), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) over 10 h. Selection of 12 C and 7 T homozygotes for the LRP exon 22 C200T polymorphism for the study also enabled us to examine the influence of this polymorphism on postprandial mRNA expression and lipoproteins, of relevance because of LRP's role in postprandial lipoprotein metabolism and association of the polymorphism with coronary artery disease. We found a postprandial decrease in LDLR mRNA abundance relative to the reference -actin (BA) mRNA. The decreased LDLR/BA mRNA value was apparent at 1 h (P < 0.005) and decreased to 25% of baseline at 6 h (P < 0.005). The LRP/BA mRNA value was also lower at 6 h (16% decrease, P < 0.05). HMGCR mRNA expression was unchanged. C homozygotes for the C200T polymorphism had higher LDLR/BA values than T homozygotes (P = 0.01) and although plasma LDL cholesterol (LDL-C) concentrations decreased in the postprandial period (P < 0.002), the decrease was less in C than in T homozygotes (P < 0.05). This study constitutes the first observation, to our knowledge, of postprandial changes in LDLR and LRP mRNA expression. It documents immediate effects of a fatty meal on these mRNA as well as an LRP genotype effect on LDLR mRNA and LDL-C. |
| first_indexed | 2025-11-14T07:23:09Z |
| format | Journal Article |
| id | curtin-20.500.11937-17850 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:23:09Z |
| publishDate | 2007 |
| publisher | American Society for Nutritional Sciences |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-178502017-05-30T08:11:13Z LDL-Receptor mRNA Expression in Men Is Downregulated within an Hour of an Acute Fat Load and Is Influenced by Genetic Polymorphism Pocathikorn, A. Taylor, R. Mamotte, Cyril Little is known about the immediate effects of dietary fat on the expression of genes involved in cholesterol metabolism in humans. We investigated the effects of a high-fat meal on circulating mononuclear cell messenger RNA (mRNA) for the LDL receptor (LDLR), LDLR-related protein (LRP), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) over 10 h. Selection of 12 C and 7 T homozygotes for the LRP exon 22 C200T polymorphism for the study also enabled us to examine the influence of this polymorphism on postprandial mRNA expression and lipoproteins, of relevance because of LRP's role in postprandial lipoprotein metabolism and association of the polymorphism with coronary artery disease. We found a postprandial decrease in LDLR mRNA abundance relative to the reference -actin (BA) mRNA. The decreased LDLR/BA mRNA value was apparent at 1 h (P < 0.005) and decreased to 25% of baseline at 6 h (P < 0.005). The LRP/BA mRNA value was also lower at 6 h (16% decrease, P < 0.05). HMGCR mRNA expression was unchanged. C homozygotes for the C200T polymorphism had higher LDLR/BA values than T homozygotes (P = 0.01) and although plasma LDL cholesterol (LDL-C) concentrations decreased in the postprandial period (P < 0.002), the decrease was less in C than in T homozygotes (P < 0.05). This study constitutes the first observation, to our knowledge, of postprandial changes in LDLR and LRP mRNA expression. It documents immediate effects of a fatty meal on these mRNA as well as an LRP genotype effect on LDLR mRNA and LDL-C. 2007 Journal Article http://hdl.handle.net/20.500.11937/17850 http://jn.nutrition.org/cgi/content/full/137/9/2062 American Society for Nutritional Sciences restricted |
| spellingShingle | Pocathikorn, A. Taylor, R. Mamotte, Cyril LDL-Receptor mRNA Expression in Men Is Downregulated within an Hour of an Acute Fat Load and Is Influenced by Genetic Polymorphism |
| title | LDL-Receptor mRNA Expression in Men Is Downregulated within an Hour of an Acute Fat Load and Is Influenced by Genetic Polymorphism |
| title_full | LDL-Receptor mRNA Expression in Men Is Downregulated within an Hour of an Acute Fat Load and Is Influenced by Genetic Polymorphism |
| title_fullStr | LDL-Receptor mRNA Expression in Men Is Downregulated within an Hour of an Acute Fat Load and Is Influenced by Genetic Polymorphism |
| title_full_unstemmed | LDL-Receptor mRNA Expression in Men Is Downregulated within an Hour of an Acute Fat Load and Is Influenced by Genetic Polymorphism |
| title_short | LDL-Receptor mRNA Expression in Men Is Downregulated within an Hour of an Acute Fat Load and Is Influenced by Genetic Polymorphism |
| title_sort | ldl-receptor mrna expression in men is downregulated within an hour of an acute fat load and is influenced by genetic polymorphism |
| url | http://jn.nutrition.org/cgi/content/full/137/9/2062 http://hdl.handle.net/20.500.11937/17850 |