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Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ

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 ar...

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Autores principales: Moldes-Anaya, Angel, Sæther, Thomas, Uhlig, Silvio, Nebb, Hilde I., Larsen, Terje, Eilertsen, Hans C., Paulsen, Steinar M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484098/
https://www.ncbi.nlm.nih.gov/pubmed/28587091
http://dx.doi.org/10.3390/md15060148
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author Moldes-Anaya, Angel
Sæther, Thomas
Uhlig, Silvio
Nebb, Hilde I.
Larsen, Terje
Eilertsen, Hans C.
Paulsen, Steinar M.
author_facet Moldes-Anaya, Angel
Sæther, Thomas
Uhlig, Silvio
Nebb, Hilde I.
Larsen, Terje
Eilertsen, Hans C.
Paulsen, Steinar M.
author_sort Moldes-Anaya, Angel
collection PubMed
description 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.
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spelling pubmed-54840982017-06-29 Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ Moldes-Anaya, Angel Sæther, Thomas Uhlig, Silvio Nebb, Hilde I. Larsen, Terje Eilertsen, Hans C. Paulsen, Steinar M. Mar Drugs Article 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. MDPI 2017-05-25 /pmc/articles/PMC5484098/ /pubmed/28587091 http://dx.doi.org/10.3390/md15060148 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Moldes-Anaya, Angel
Sæther, Thomas
Uhlig, Silvio
Nebb, Hilde I.
Larsen, Terje
Eilertsen, Hans C.
Paulsen, Steinar M.
Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ
title Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ
title_full Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ
title_fullStr Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ
title_full_unstemmed Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ
title_short Two Isomeric C16 Oxo-Fatty Acids from the Diatom Chaetoceros karianus Show Dual Agonist Activity towards Human Peroxisome Proliferator-Activated Receptors (PPARs) α/γ
title_sort two isomeric c16 oxo-fatty acids from the diatom chaetoceros karianus show dual agonist activity towards human peroxisome proliferator-activated receptors (ppars) α/γ
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5484098/
https://www.ncbi.nlm.nih.gov/pubmed/28587091
http://dx.doi.org/10.3390/md15060148
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