Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model
Hypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed t...
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2016-01-01
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| Series: | Journal of Nutritional Science |
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| Online Access: | https://www.cambridge.org/core/product/identifier/S2048679016000033/type/journal_article |
| _version_ | 1811155958274981888 |
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| author | Haiqiu Huang Zhuohong Xie Wallace Yokoyama Liangli Yu Thomas T. Y. Wang |
| author_facet | Haiqiu Huang Zhuohong Xie Wallace Yokoyama Liangli Yu Thomas T. Y. Wang |
| author_sort | Haiqiu Huang |
| collection | DOAJ |
| description | Hypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed to gain more comprehensive understanding of the relationship between circulating cholesterol levels and molecular effects in target tissues using the hamster model. Male golden Syrian hamsters were fed with chow or diets containing 36 % energy from fat with or without 1 % cholesteyramine (CA) as a modulator of circulating cholesterol levels for 35 d. It was revealed that the expression of lanosterol 14α-demethylase (CYP51) instead of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression was responsive to circulating cholesterol in hamsters fed hypercholesterolaemic diets. The high-fat diet increased circulating cholesterol and down-regulated CYP51, but not HMG-CoA reductase. The CA diet decreased cholesterol and increased CYP51 expression, but HMG-CoA reductase expression was not affected. The high-fat diet and CA diet altered the expression level of cholesterol, bile acids and lipid metabolism-associated genes (LDL receptor, cholesterol 7α-hydroxylase (CYP7A1), liver X receptor (LXR) α, and ATP-binding cassette subfamily G member 5/8 (ABCG5/8)) in the liver, which were significantly correlated with circulating cholesterol levels. Correlation analysis also showed that circulating cholesterol levels were regulated by LXR/retinoid X receptor and PPAR pathways in the liver. Using the hamster model, the present study provided additional molecular insights into the influence of circulating cholesterol on hepatic cholesterol metabolism pathways during hypercholesterolaemia. |
| first_indexed | 2024-04-10T04:43:30Z |
| format | Article |
| id | doaj.art-f815573b771c4bddaca145aa3fe75227 |
| institution | Directory Open Access Journal |
| issn | 2048-6790 |
| language | English |
| last_indexed | 2024-04-10T04:43:30Z |
| publishDate | 2016-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Nutritional Science |
| spelling | doaj.art-f815573b771c4bddaca145aa3fe752272023-03-09T12:38:50ZengCambridge University PressJournal of Nutritional Science2048-67902016-01-01510.1017/jns.2016.3Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster modelHaiqiu Huang0Zhuohong Xie1Wallace Yokoyama2Liangli Yu3Thomas T. Y. Wang4Diet, Genomics and Immunology Laboratory, USDA-ARS, Beltsville, MD 20705, USAInternational Chemistry Testing, Milford, MA 01757, USAProcessed Foods Research, USDA-ARS, Albany, CA 94710, USADepartment of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USADiet, Genomics and Immunology Laboratory, USDA-ARS, Beltsville, MD 20705, USAHypercholesterolaemia is a risk factor for CVD, which is a leading cause of death in industrialised societies. The biosynthetic pathways for cholesterol metabolism are well understood; however, the regulation of circulating cholesterol by diet is still not fully elucidated. The present study aimed to gain more comprehensive understanding of the relationship between circulating cholesterol levels and molecular effects in target tissues using the hamster model. Male golden Syrian hamsters were fed with chow or diets containing 36 % energy from fat with or without 1 % cholesteyramine (CA) as a modulator of circulating cholesterol levels for 35 d. It was revealed that the expression of lanosterol 14α-demethylase (CYP51) instead of 3-hydroxy-3-methyl-glutaryl (HMG)-CoA reductase mRNA expression was responsive to circulating cholesterol in hamsters fed hypercholesterolaemic diets. The high-fat diet increased circulating cholesterol and down-regulated CYP51, but not HMG-CoA reductase. The CA diet decreased cholesterol and increased CYP51 expression, but HMG-CoA reductase expression was not affected. The high-fat diet and CA diet altered the expression level of cholesterol, bile acids and lipid metabolism-associated genes (LDL receptor, cholesterol 7α-hydroxylase (CYP7A1), liver X receptor (LXR) α, and ATP-binding cassette subfamily G member 5/8 (ABCG5/8)) in the liver, which were significantly correlated with circulating cholesterol levels. Correlation analysis also showed that circulating cholesterol levels were regulated by LXR/retinoid X receptor and PPAR pathways in the liver. Using the hamster model, the present study provided additional molecular insights into the influence of circulating cholesterol on hepatic cholesterol metabolism pathways during hypercholesterolaemia.https://www.cambridge.org/core/product/identifier/S2048679016000033/type/journal_articleCirculating cholesterol CYP51 HamstersHypercholesterolaemia |
| spellingShingle | Haiqiu Huang Zhuohong Xie Wallace Yokoyama Liangli Yu Thomas T. Y. Wang Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model Journal of Nutritional Science Circulating cholesterol CYP51 Hamsters Hypercholesterolaemia |
| title | Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model |
| title_full | Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model |
| title_fullStr | Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model |
| title_full_unstemmed | Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model |
| title_short | Identification of liver CYP51 as a gene responsive to circulating cholesterol in a hamster model |
| title_sort | identification of liver cyp51 as a gene responsive to circulating cholesterol in a hamster model |
| topic | Circulating cholesterol CYP51 Hamsters Hypercholesterolaemia |
| url | https://www.cambridge.org/core/product/identifier/S2048679016000033/type/journal_article |
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