title: Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile.
abstract: 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.
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Mattijs M
authors.initials: MM
authors.lastname: Heemskerk
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Harish K
authors.initials: HK
authors.lastname: Dharuri
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Sjoerd A A
authors.initials: SA
authors.lastname: van den Berg
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Hulda S
authors.initials: HS
authors.lastname: Jónasdóttir
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Dick-Paul
authors.initials: DP
authors.lastname: Kloos
authors.affiliation: Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: Giera
authors.affiliation: Department 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 Netherlands.
authors.forename: Ko Willems
authors.initials: KW
authors.lastname: van Dijk
authors.affiliation: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Vanessa
authors.initials: V
authors.lastname: van Harmelen
mesh_terms: D000465:Algorithms; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D053318:Apolipoprotein E3 / Q000235:genetics / Q000378:metabolism; D016718:Arachidonic Acid / Q000097:blood / Q000378:metabolism; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics / Q000378:metabolism; D066273:Diet, Western / Q000009:adverse effects; D004281:Docosahexaenoic Acids / Q000097:blood / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000097:blood* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000097:blood / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006900:Hydroxylation; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008822:Mice, Transgenic; D009525:Niacin / Q000494:pharmacology / Q000627:therapeutic use*; D054883:Oxylipins / Q000097:blood* / Q000378:metabolism; D013997:Time Factors
chemical_list: C000602093:19,20-dihydroxydocosapentaenoic acid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D053318:Apolipoprotein E3; D015415:Biomarkers; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D000960:Hypolipidemic Agents; D054883:Oxylipins; C052720:apolipoprotein E3 (Leidein); D004281:Docosahexaenoic Acids; D009525:Niacin; D016718:Arachidonic Acid
keywords: adipocytes; cytochrome P450; drug therapy/hypolipidemic drugs; fatty acid/biosynthesis; omega-3 fatty acids; polyunsaturated fatty acid