An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro
Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglycer...
Gespeichert in:
| Veröffentlicht in: | PloS one 2018-01, Vol.13 (1), p.e0190210-e0190210 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | e0190210 |
|---|---|
| container_issue | 1 |
| container_start_page | e0190210 |
| container_title | PloS one |
| container_volume | 13 |
| creator | Alfaro-Viquez, Emilia Roling, Brent F Krueger, Christian G Rainey, Charlene J Reed, Jess D Ricketts, Marie-Louise |
| description | Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglyceride and cholesterol homeostasis. Freeze-dried extracts were isolated from California-grown dates (Deglet Noor and Medjool) from the 2014 and 2015 harvests, by means of liquid extraction and solid phase separation. Each date palm extract (DPE) was characterized via HPLC and MALDI-TOF mass spectrometry, and the procyanidin content was qualitatively determined. Extracts were tested to determine their ability to modulate nuclear receptor-mediated transactivation using transient transfection. The effect of DPE on FXR-target genes regulating bile acid absorption and transport was then assessed in vitro, in Caco-2 cells. Characterization reveals that DPE is a rich source of polyphenols including hydroxycinnamic acids, proanthocyanidins, and lipohilic polyphenols, and comprises 13% proanthocyanidins. Transactivation results show that DPE acts as a co-agonist ligand for both mouse and human FXR, wherein it activates bile acid-bound FXR greater than that seen with bile acid alone. Additionally, DPE alone activated a peroxisome proliferator activated receptor alpha (PPARα) chimera in a dose-dependent manner. Consistent with DPE as a co-agonist ligand for FXR, studies in Caco-2 cells reveal that co-incubation with bile acid, dose-dependently enhances the expression of fibroblast growth factor 19 (FGF19), compared to treatment with bile acid alone. In contrast, DPE inhibited bile acid-induced expression of ileal bile acid binding protein (IBABP). Our results demonstrate that DPE acts as a potent co-agonist ligand for FXR, and that it differentially regulates FXR-target gene expression in vitro in human intestinal cells. This study provides novel insight into a potential mechanism by which dates may exert a hypotriglyceridemic effect via FXR and modulation of bile acid homeostasis. |
| doi_str_mv | 10.1371/journal.pone.0190210 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1983901597</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A521120034</galeid><doaj_id>oai_doaj_org_article_e0db08639d0a49c3bf6bb89fd1f7385e</doaj_id><sourcerecordid>A521120034</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5080-5f5d77573998d78b41d7063bb0b19fc5bb3f7d3dcba9a5ba6fa92b84382b93da3</originalsourceid><addsrcrecordid>eNptUl1rFDEUHUSxdfUfiAZ8qQ-7JpPJZPJSKMVqoaCIgm8hn9OUTLImmdL-Kv-i2e22dKUkkJt7zz33g9M0bxFcIUzRp6s4pyD8ah2DWUHEYIvgs-YQMdwu-xbi54_sg-ZVzlcQEjz0_cvmoGUtw4Syw-bvSQDmpiShCrApTkCLYsBa-Kl-Z1fA0ffLaIK7qQFVbr2zJomPoNoZiHqBiksxxuByAd6NImhgYwLl0oAwK29EAskosy7Vefb7B9gAtLOVxYTihPe3YIp69rVq3gKKSKMpy9EEUxtbJ5OziwG4AK5dSfF188IKn82b3btofp19_nn6dXnx7cv56cnFUhE4wCWxRFNKKGZs0HSQHdIU9lhKKBGzikiJLdVYKymYIFL0VrBWDh0eWsmwFnjRvL_jXfuY-W7XmSM2YAYRYbQizu8QOoorvk5uEumWR-H41hHTyEUqru6AG6glHHrMNBQdU1jaXsqBWY0sxQMxlet4V22Wk9Gq7iYJv0e6Hwnuko_xmhPaMUpxJTjaEaT4Zza58MllZbwXwcR523fXkravilg0H_6DPj3dDjWKOoALNm40siHlJ6RFqIUQdxW1egJVjzaTU1WY1lX_XkJ3l6BSzDkZ-zAjgnwj6_tm-EbWfCfrmvbu8X4eku51jP8Bz8X36A</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1983901597</pqid></control><display><type>article</type><title>An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro</title><source>PMC (PubMed Central)</source><source>Directory of Open Access Journals</source><source>Public Library of Science</source><source>Free Full-Text Journals in Chemistry</source><source>EZB Electronic Journals Library</source><creator>Alfaro-Viquez, Emilia ; Roling, Brent F ; Krueger, Christian G ; Rainey, Charlene J ; Reed, Jess D ; Ricketts, Marie-Louise</creator><contributor>Cooney, Austin John</contributor><creatorcontrib>Alfaro-Viquez, Emilia ; Roling, Brent F ; Krueger, Christian G ; Rainey, Charlene J ; Reed, Jess D ; Ricketts, Marie-Louise ; Cooney, Austin John</creatorcontrib><description>Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglyceride and cholesterol homeostasis. Freeze-dried extracts were isolated from California-grown dates (Deglet Noor and Medjool) from the 2014 and 2015 harvests, by means of liquid extraction and solid phase separation. Each date palm extract (DPE) was characterized via HPLC and MALDI-TOF mass spectrometry, and the procyanidin content was qualitatively determined. Extracts were tested to determine their ability to modulate nuclear receptor-mediated transactivation using transient transfection. The effect of DPE on FXR-target genes regulating bile acid absorption and transport was then assessed in vitro, in Caco-2 cells. Characterization reveals that DPE is a rich source of polyphenols including hydroxycinnamic acids, proanthocyanidins, and lipohilic polyphenols, and comprises 13% proanthocyanidins. Transactivation results show that DPE acts as a co-agonist ligand for both mouse and human FXR, wherein it activates bile acid-bound FXR greater than that seen with bile acid alone. Additionally, DPE alone activated a peroxisome proliferator activated receptor alpha (PPARα) chimera in a dose-dependent manner. Consistent with DPE as a co-agonist ligand for FXR, studies in Caco-2 cells reveal that co-incubation with bile acid, dose-dependently enhances the expression of fibroblast growth factor 19 (FGF19), compared to treatment with bile acid alone. In contrast, DPE inhibited bile acid-induced expression of ileal bile acid binding protein (IBABP). Our results demonstrate that DPE acts as a potent co-agonist ligand for FXR, and that it differentially regulates FXR-target gene expression in vitro in human intestinal cells. This study provides novel insight into a potential mechanism by which dates may exert a hypotriglyceridemic effect via FXR and modulation of bile acid homeostasis.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0190210</identifier><identifier>PMID: 29293579</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Bile ; Biology and Life Sciences ; Cell receptors ; Cholesterol ; Date (Fruit) ; Fibroblast growth factor ; Fibroblast growth factors ; Fruits ; Gene expression ; Health aspects ; High-performance liquid chromatography ; Homeostasis ; Hydroxycinnamic acid ; Incubation ; Intestine ; Ligands ; Lipid metabolism ; Liquid chromatography ; Mass spectrometry ; Mass spectroscopy ; Medicine and Health Sciences ; Nutrition ; Phase separation ; Phoenix dactylifera ; Physical Sciences ; Plant extracts ; Polyphenols ; Proanthocyanidins ; Research and Analysis Methods ; Transfection</subject><ispartof>PloS one, 2018-01, Vol.13 (1), p.e0190210-e0190210</ispartof><rights>COPYRIGHT 2018 Public Library of Science</rights><rights>2018 Alfaro-Viquez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2018 Alfaro-Viquez et al 2018 Alfaro-Viquez et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5080-5f5d77573998d78b41d7063bb0b19fc5bb3f7d3dcba9a5ba6fa92b84382b93da3</citedby><cites>FETCH-LOGICAL-c5080-5f5d77573998d78b41d7063bb0b19fc5bb3f7d3dcba9a5ba6fa92b84382b93da3</cites><orcidid>0000-0002-8306-7563</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749773/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5749773/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29293579$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Cooney, Austin John</contributor><creatorcontrib>Alfaro-Viquez, Emilia</creatorcontrib><creatorcontrib>Roling, Brent F</creatorcontrib><creatorcontrib>Krueger, Christian G</creatorcontrib><creatorcontrib>Rainey, Charlene J</creatorcontrib><creatorcontrib>Reed, Jess D</creatorcontrib><creatorcontrib>Ricketts, Marie-Louise</creatorcontrib><title>An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglyceride and cholesterol homeostasis. Freeze-dried extracts were isolated from California-grown dates (Deglet Noor and Medjool) from the 2014 and 2015 harvests, by means of liquid extraction and solid phase separation. Each date palm extract (DPE) was characterized via HPLC and MALDI-TOF mass spectrometry, and the procyanidin content was qualitatively determined. Extracts were tested to determine their ability to modulate nuclear receptor-mediated transactivation using transient transfection. The effect of DPE on FXR-target genes regulating bile acid absorption and transport was then assessed in vitro, in Caco-2 cells. Characterization reveals that DPE is a rich source of polyphenols including hydroxycinnamic acids, proanthocyanidins, and lipohilic polyphenols, and comprises 13% proanthocyanidins. Transactivation results show that DPE acts as a co-agonist ligand for both mouse and human FXR, wherein it activates bile acid-bound FXR greater than that seen with bile acid alone. Additionally, DPE alone activated a peroxisome proliferator activated receptor alpha (PPARα) chimera in a dose-dependent manner. Consistent with DPE as a co-agonist ligand for FXR, studies in Caco-2 cells reveal that co-incubation with bile acid, dose-dependently enhances the expression of fibroblast growth factor 19 (FGF19), compared to treatment with bile acid alone. In contrast, DPE inhibited bile acid-induced expression of ileal bile acid binding protein (IBABP). Our results demonstrate that DPE acts as a potent co-agonist ligand for FXR, and that it differentially regulates FXR-target gene expression in vitro in human intestinal cells. This study provides novel insight into a potential mechanism by which dates may exert a hypotriglyceridemic effect via FXR and modulation of bile acid homeostasis.</description><subject>Acids</subject><subject>Bile</subject><subject>Biology and Life Sciences</subject><subject>Cell receptors</subject><subject>Cholesterol</subject><subject>Date (Fruit)</subject><subject>Fibroblast growth factor</subject><subject>Fibroblast growth factors</subject><subject>Fruits</subject><subject>Gene expression</subject><subject>Health aspects</subject><subject>High-performance liquid chromatography</subject><subject>Homeostasis</subject><subject>Hydroxycinnamic acid</subject><subject>Incubation</subject><subject>Intestine</subject><subject>Ligands</subject><subject>Lipid metabolism</subject><subject>Liquid chromatography</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Medicine and Health Sciences</subject><subject>Nutrition</subject><subject>Phase separation</subject><subject>Phoenix dactylifera</subject><subject>Physical Sciences</subject><subject>Plant extracts</subject><subject>Polyphenols</subject><subject>Proanthocyanidins</subject><subject>Research and Analysis Methods</subject><subject>Transfection</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNptUl1rFDEUHUSxdfUfiAZ8qQ-7JpPJZPJSKMVqoaCIgm8hn9OUTLImmdL-Kv-i2e22dKUkkJt7zz33g9M0bxFcIUzRp6s4pyD8ah2DWUHEYIvgs-YQMdwu-xbi54_sg-ZVzlcQEjz0_cvmoGUtw4Syw-bvSQDmpiShCrApTkCLYsBa-Kl-Z1fA0ffLaIK7qQFVbr2zJomPoNoZiHqBiksxxuByAd6NImhgYwLl0oAwK29EAskosy7Vefb7B9gAtLOVxYTihPe3YIp69rVq3gKKSKMpy9EEUxtbJ5OziwG4AK5dSfF188IKn82b3btofp19_nn6dXnx7cv56cnFUhE4wCWxRFNKKGZs0HSQHdIU9lhKKBGzikiJLdVYKymYIFL0VrBWDh0eWsmwFnjRvL_jXfuY-W7XmSM2YAYRYbQizu8QOoorvk5uEumWR-H41hHTyEUqru6AG6glHHrMNBQdU1jaXsqBWY0sxQMxlet4V22Wk9Gq7iYJv0e6Hwnuko_xmhPaMUpxJTjaEaT4Zza58MllZbwXwcR523fXkravilg0H_6DPj3dDjWKOoALNm40siHlJ6RFqIUQdxW1egJVjzaTU1WY1lX_XkJ3l6BSzDkZ-zAjgnwj6_tm-EbWfCfrmvbu8X4eku51jP8Bz8X36A</recordid><startdate>20180101</startdate><enddate>20180101</enddate><creator>Alfaro-Viquez, Emilia</creator><creator>Roling, Brent F</creator><creator>Krueger, Christian G</creator><creator>Rainey, Charlene J</creator><creator>Reed, Jess D</creator><creator>Ricketts, Marie-Louise</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8306-7563</orcidid></search><sort><creationdate>20180101</creationdate><title>An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro</title><author>Alfaro-Viquez, Emilia ; Roling, Brent F ; Krueger, Christian G ; Rainey, Charlene J ; Reed, Jess D ; Ricketts, Marie-Louise</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5080-5f5d77573998d78b41d7063bb0b19fc5bb3f7d3dcba9a5ba6fa92b84382b93da3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Acids</topic><topic>Bile</topic><topic>Biology and Life Sciences</topic><topic>Cell receptors</topic><topic>Cholesterol</topic><topic>Date (Fruit)</topic><topic>Fibroblast growth factor</topic><topic>Fibroblast growth factors</topic><topic>Fruits</topic><topic>Gene expression</topic><topic>Health aspects</topic><topic>High-performance liquid chromatography</topic><topic>Homeostasis</topic><topic>Hydroxycinnamic acid</topic><topic>Incubation</topic><topic>Intestine</topic><topic>Ligands</topic><topic>Lipid metabolism</topic><topic>Liquid chromatography</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Medicine and Health Sciences</topic><topic>Nutrition</topic><topic>Phase separation</topic><topic>Phoenix dactylifera</topic><topic>Physical Sciences</topic><topic>Plant extracts</topic><topic>Polyphenols</topic><topic>Proanthocyanidins</topic><topic>Research and Analysis Methods</topic><topic>Transfection</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alfaro-Viquez, Emilia</creatorcontrib><creatorcontrib>Roling, Brent F</creatorcontrib><creatorcontrib>Krueger, Christian G</creatorcontrib><creatorcontrib>Rainey, Charlene J</creatorcontrib><creatorcontrib>Reed, Jess D</creatorcontrib><creatorcontrib>Ricketts, Marie-Louise</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>ProQuest Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>Biological Sciences</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest advanced technologies & aerospace journals</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alfaro-Viquez, Emilia</au><au>Roling, Brent F</au><au>Krueger, Christian G</au><au>Rainey, Charlene J</au><au>Reed, Jess D</au><au>Ricketts, Marie-Louise</au><au>Cooney, Austin John</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2018-01-01</date><risdate>2018</risdate><volume>13</volume><issue>1</issue><spage>e0190210</spage><epage>e0190210</epage><pages>e0190210-e0190210</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Date palm fruit (Phoenix dactylifera) consumption reduces serum triglyceride levels in human subjects. The objective of this study was to prepare an extract from dates and determine whether it acts as a ligand for the farnesoid x receptor (FXR), a nuclear receptor important for maintaining triglyceride and cholesterol homeostasis. Freeze-dried extracts were isolated from California-grown dates (Deglet Noor and Medjool) from the 2014 and 2015 harvests, by means of liquid extraction and solid phase separation. Each date palm extract (DPE) was characterized via HPLC and MALDI-TOF mass spectrometry, and the procyanidin content was qualitatively determined. Extracts were tested to determine their ability to modulate nuclear receptor-mediated transactivation using transient transfection. The effect of DPE on FXR-target genes regulating bile acid absorption and transport was then assessed in vitro, in Caco-2 cells. Characterization reveals that DPE is a rich source of polyphenols including hydroxycinnamic acids, proanthocyanidins, and lipohilic polyphenols, and comprises 13% proanthocyanidins. Transactivation results show that DPE acts as a co-agonist ligand for both mouse and human FXR, wherein it activates bile acid-bound FXR greater than that seen with bile acid alone. Additionally, DPE alone activated a peroxisome proliferator activated receptor alpha (PPARα) chimera in a dose-dependent manner. Consistent with DPE as a co-agonist ligand for FXR, studies in Caco-2 cells reveal that co-incubation with bile acid, dose-dependently enhances the expression of fibroblast growth factor 19 (FGF19), compared to treatment with bile acid alone. In contrast, DPE inhibited bile acid-induced expression of ileal bile acid binding protein (IBABP). Our results demonstrate that DPE acts as a potent co-agonist ligand for FXR, and that it differentially regulates FXR-target gene expression in vitro in human intestinal cells. This study provides novel insight into a potential mechanism by which dates may exert a hypotriglyceridemic effect via FXR and modulation of bile acid homeostasis.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29293579</pmid><doi>10.1371/journal.pone.0190210</doi><orcidid>https://orcid.org/0000-0002-8306-7563</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2018-01, Vol.13 (1), p.e0190210-e0190210 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1983901597 |
| source | PMC (PubMed Central); Directory of Open Access Journals; Public Library of Science; Free Full-Text Journals in Chemistry; EZB Electronic Journals Library |
| subjects | Acids Bile Biology and Life Sciences Cell receptors Cholesterol Date (Fruit) Fibroblast growth factor Fibroblast growth factors Fruits Gene expression Health aspects High-performance liquid chromatography Homeostasis Hydroxycinnamic acid Incubation Intestine Ligands Lipid metabolism Liquid chromatography Mass spectrometry Mass spectroscopy Medicine and Health Sciences Nutrition Phase separation Phoenix dactylifera Physical Sciences Plant extracts Polyphenols Proanthocyanidins Research and Analysis Methods Transfection |
| title | An extract from date palm fruit (Phoenix dactylifera) acts as a co-agonist ligand for the nuclear receptor FXR and differentially modulates FXR target-gene expression in vitro |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-24T19%3A41%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20extract%20from%20date%20palm%20fruit%20(Phoenix%20dactylifera)%20acts%20as%20a%20co-agonist%20ligand%20for%20the%20nuclear%20receptor%20FXR%20and%20differentially%20modulates%20FXR%20target-gene%20expression%20in%20vitro&rft.jtitle=PloS%20one&rft.au=Alfaro-Viquez,%20Emilia&rft.date=2018-01-01&rft.volume=13&rft.issue=1&rft.spage=e0190210&rft.epage=e0190210&rft.pages=e0190210-e0190210&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0190210&rft_dat=%3Cgale_plos_%3EA521120034%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1983901597&rft_id=info:pmid/29293579&rft_galeid=A521120034&rft_doaj_id=oai_doaj_org_article_e0db08639d0a49c3bf6bb89fd1f7385e&rfr_iscdi=true |