Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ
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- Angel Moldes-Anaya
- Cardiovascular Research Group, Department of Medical Biology, UiT The Arctic University of Norway, 9019 Tromsø, Norway
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- Thomas Sæther
- Cardiovascular Research Group, Department of Medical Biology, UiT The Arctic University of Norway, 9019 Tromsø, Norway
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- Silvio Uhlig
- Section for Chemistry, Norwegian Veterinary Institute, 0106 Oslo, Norway
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- Hilde Nebb
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, 0313 Oslo, Norway
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- Terje Larsen
- Cardiovascular Research Group, Department of Medical Biology, UiT The Arctic University of Norway, 9019 Tromsø, Norway
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- Hans Eilertsen
- Norwegian College of Fishery Science, UiT The Arctic University of Norway, 9019 Tromsø, Norway
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- Steinar Paulsen
- MabCent-SFI, UiT The Arctic University of Norway, 9019 Tromsø, Norway
説明
<jats:p>The peroxisome proliferator-activated receptors (PPARs) function as ligand-activated transcription factors that convert signals in the form of lipids to physiological responses through the activation of metabolic target genes. Due to their key roles in lipid and carbohydrate metabolism, the PPARs are important drug targets. However, for several of the PPAR drugs currently in use, adverse side effects have been reported. In an effort to identify compounds from marine organisms that may serve as molecular scaffolds for the development of novel and safer PPAR-targeting drugs, we performed a bioassay-guided screening of organic extracts made from organisms supplied by the Norwegian Biobank of Arctic Marine Organisms (Marbank). Among several interesting hits, we identified two poorly described isomeric oxo-fatty acids from the microalgae Chaetoceros karianus for which we provide the first evidence that they might display dual specificity towards human PPARα and PPARγ. Principal component analysis showed that C. karianus stood out from other Chaetoceros species, both with respect to the metabolic profile and the PPAR activity. The isolation of these compounds holds the potential of uncovering a PPAR pharmacophore with tunable activity and specificity.</jats:p>
収録刊行物
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- Marine Drugs
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Marine Drugs 15 (6), 148-, 2017-05-25
MDPI AG
