Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S]
Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, b...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2014-12-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520366931 |
| _version_ | 1818381571522035712 |
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| author | Mattijs M. Heemskerk Harish K. Dharuri Sjoerd A.A. van den Berg Hulda S. Jónasdóttir Dick-Paul Kloos Martin Giera Ko Willems van Dijk Vanessa van Harmelen |
| author_facet | Mattijs M. Heemskerk Harish K. Dharuri Sjoerd A.A. van den Berg Hulda S. Jónasdóttir Dick-Paul Kloos Martin Giera Ko Willems van Dijk Vanessa van Harmelen |
| author_sort | Mattijs M. Heemskerk |
| collection | DOAJ |
| description | Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the “biosynthesis of unsaturated fatty acids” pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment. |
| first_indexed | 2024-12-14T02:36:42Z |
| format | Article |
| id | doaj.art-cf7bbab231594b41b33465b0ea0b8fa8 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-14T02:36:42Z |
| publishDate | 2014-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-cf7bbab231594b41b33465b0ea0b8fa82022-12-21T23:20:07ZengElsevierJournal of Lipid Research0022-22752014-12-01551225322540Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S]Mattijs M. Heemskerk0Harish K. Dharuri1Sjoerd A.A. van den Berg2Hulda S. Jónasdóttir3Dick-Paul Kloos4Martin Giera5Ko Willems van Dijk6Vanessa van Harmelen7Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The NetherlandsCenter for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Internal Medicine, Leiden University Medical Center, Leiden, The NetherlandsTo whom correspondence should be addressed; Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; To whom correspondence should be addressedProlonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the “biosynthesis of unsaturated fatty acids” pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment.http://www.sciencedirect.com/science/article/pii/S0022227520366931drug therapy/hypolipidemic drugsadipocytesfatty acid/biosynthesisomega-3 fatty acidscytochrome P450polyunsaturated fatty acid |
| spellingShingle | Mattijs M. Heemskerk Harish K. Dharuri Sjoerd A.A. van den Berg Hulda S. Jónasdóttir Dick-Paul Kloos Martin Giera Ko Willems van Dijk Vanessa van Harmelen Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S] Journal of Lipid Research drug therapy/hypolipidemic drugs adipocytes fatty acid/biosynthesis omega-3 fatty acids cytochrome P450 polyunsaturated fatty acid |
| title | Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S] |
| title_full | Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S] |
| title_fullStr | Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S] |
| title_full_unstemmed | Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S] |
| title_short | Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile[S] |
| title_sort | prolonged niacin treatment leads to increased adipose tissue pufa synthesis and anti inflammatory lipid and oxylipin plasma profile s |
| topic | drug therapy/hypolipidemic drugs adipocytes fatty acid/biosynthesis omega-3 fatty acids cytochrome P450 polyunsaturated fatty acid |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520366931 |
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