Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil
Cancer treatment evokes impediments to liver metabolism that culminate in fatty liver. This study determined hepatic fatty acid composition and expression of genes and mediators involved in lipid metabolism following chemotherapy treatment. Female rats bearing the Ward colon tumor were administered...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3547 |
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| author | Md Monirujjaman Leila Baghersad Renani Peter Isesele Abha R. Dunichand-Hoedl Vera C. Mazurak |
| author_facet | Md Monirujjaman Leila Baghersad Renani Peter Isesele Abha R. Dunichand-Hoedl Vera C. Mazurak |
| author_sort | Md Monirujjaman |
| collection | DOAJ |
| description | Cancer treatment evokes impediments to liver metabolism that culminate in fatty liver. This study determined hepatic fatty acid composition and expression of genes and mediators involved in lipid metabolism following chemotherapy treatment. Female rats bearing the Ward colon tumor were administered Irinotecan (CPT-11) +5-fluorouracil (5-FU) and maintained on a control diet or a diet containing eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (2.3 g/100 g fish oil). Healthy animals provided with a control diet served as a reference group. Livers were collected one week after chemotherapy. Triacylglycerol (TG), phospholipid (PL), ten lipid metabolism genes, leptin, and IL-4 were measured. Chemotherapy increased TG content and reduced EPA content in the liver. Expression of SCD1 was upregulated by chemotherapy, while dietary fish oil downregulated its expression. Dietary fish oil down-regulated expression of the fatty acid synthesis gene FASN, while restoring the long chain fatty acid converting genes FADS2 and ELOVL2, and genes involved in mitochondrial β-oxidation (CPT1α) and lipid transport (MTTP1), to values similar to reference animals. Neither leptin nor IL-4 were affected by chemotherapy or diet. Depletion of EPA is associated with pathways evoking enhanced TG accumulation in the liver. Restoring EPA through diet may pose a dietary strategy to attenuate chemotherapy-associated impediments in liver fatty acid metabolism. |
| first_indexed | 2024-03-11T08:43:28Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T08:43:28Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e63333ffc0734a78b5e7920f7262b0ce2023-11-16T21:01:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244354710.3390/ijms24043547Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish OilMd Monirujjaman0Leila Baghersad Renani1Peter Isesele2Abha R. Dunichand-Hoedl3Vera C. Mazurak4Division of Human Nutrition, Department of Agricultural Food and Nutritional Science, Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB T6G 2P5, CanadaDivision of Human Nutrition, Department of Agricultural Food and Nutritional Science, Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB T6G 2P5, CanadaDivision of Human Nutrition, Department of Agricultural Food and Nutritional Science, Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB T6G 2P5, CanadaDivision of Human Nutrition, Department of Agricultural Food and Nutritional Science, Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB T6G 2P5, CanadaDivision of Human Nutrition, Department of Agricultural Food and Nutritional Science, Li Ka Shing Centre for Health Research Innovation, University of Alberta, Edmonton, AB T6G 2P5, CanadaCancer treatment evokes impediments to liver metabolism that culminate in fatty liver. This study determined hepatic fatty acid composition and expression of genes and mediators involved in lipid metabolism following chemotherapy treatment. Female rats bearing the Ward colon tumor were administered Irinotecan (CPT-11) +5-fluorouracil (5-FU) and maintained on a control diet or a diet containing eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) (2.3 g/100 g fish oil). Healthy animals provided with a control diet served as a reference group. Livers were collected one week after chemotherapy. Triacylglycerol (TG), phospholipid (PL), ten lipid metabolism genes, leptin, and IL-4 were measured. Chemotherapy increased TG content and reduced EPA content in the liver. Expression of SCD1 was upregulated by chemotherapy, while dietary fish oil downregulated its expression. Dietary fish oil down-regulated expression of the fatty acid synthesis gene FASN, while restoring the long chain fatty acid converting genes FADS2 and ELOVL2, and genes involved in mitochondrial β-oxidation (CPT1α) and lipid transport (MTTP1), to values similar to reference animals. Neither leptin nor IL-4 were affected by chemotherapy or diet. Depletion of EPA is associated with pathways evoking enhanced TG accumulation in the liver. Restoring EPA through diet may pose a dietary strategy to attenuate chemotherapy-associated impediments in liver fatty acid metabolism.https://www.mdpi.com/1422-0067/24/4/3547chemotherapycolorectal cancerCASSHfatty liveririnotecann-3 PUFA |
| spellingShingle | Md Monirujjaman Leila Baghersad Renani Peter Isesele Abha R. Dunichand-Hoedl Vera C. Mazurak Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil International Journal of Molecular Sciences chemotherapy colorectal cancer CASSH fatty liver irinotecan n-3 PUFA |
| title | Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil |
| title_full | Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil |
| title_fullStr | Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil |
| title_full_unstemmed | Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil |
| title_short | Increased Expression of Hepatic Stearoyl-CoA Desaturase (SCD)-1 and Depletion of Eicosapentaenoic Acid (EPA) Content following Cytotoxic Cancer Therapy Are Reversed by Dietary Fish Oil |
| title_sort | increased expression of hepatic stearoyl coa desaturase scd 1 and depletion of eicosapentaenoic acid epa content following cytotoxic cancer therapy are reversed by dietary fish oil |
| topic | chemotherapy colorectal cancer CASSH fatty liver irinotecan n-3 PUFA |
| url | https://www.mdpi.com/1422-0067/24/4/3547 |
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