Sensing of fatty acids for octanoylation of ghrelin involves a gustatory G-protein
Ghrelin is an important regulator of energy--and glucose homeostasis. The octanoylation at Ser(3) is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid rec...
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| Veröffentlicht in: | PloS one 2012-06, Vol.7 (6), p.e40168 |
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| description | Ghrelin is an important regulator of energy--and glucose homeostasis. The octanoylation at Ser(3) is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell.
Wild-type (WT) and α-gustducin knockout (gust(-/-)) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo.
Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/-) mice. Gastric emptying was accelerated in WT but not in gust(-/-) mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels.
This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell. |
| doi_str_mv | 10.1371/journal.pone.0040168 |
| format | Article |
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Wild-type (WT) and α-gustducin knockout (gust(-/-)) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo.
Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/-) mice. Gastric emptying was accelerated in WT but not in gust(-/-) mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels.
This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0040168</identifier><identifier>PMID: 22768248</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Agouti-Related Protein - genetics ; Agouti-Related Protein - metabolism ; alpha-Linolenic Acid - pharmacology ; Animals ; Biological effects ; Biology ; Body Weight - drug effects ; Caprylates - administration & dosage ; Caprylates - metabolism ; Caprylates - pharmacology ; Cell Line ; Chains ; Detection ; Diet ; Duodenum ; Emptying ; Fatty acids ; Fatty Acids - metabolism ; Feeding Behavior - drug effects ; Fluorescent Antibody Technique ; Food ; Gastric emptying ; Gene Expression Regulation - drug effects ; Ghrelin ; Ghrelin - metabolism ; Gnat3 protein ; Heterotrimeric GTP-Binding Proteins - metabolism ; Homeostasis ; Humans ; Immunofluorescence ; Linolenic acid ; Linolenic acids ; Lipids ; Localization ; Male ; Medical research ; Medicine ; Mice ; Mice, Inbred C57BL ; Motility ; Octanoic acid ; Oils & fats ; Omega 3 fatty acids ; Oral administration ; Palmitic Acids - pharmacology ; Peptides ; Protein Transport - drug effects ; Proteins ; Receptors ; Receptors, G-Protein-Coupled - metabolism ; RNA, Messenger - genetics ; RNA, Messenger - metabolism ; Rodents ; Saturated fatty acids ; siRNA ; Stomach ; Taste - drug effects ; Transducin</subject><ispartof>PloS one, 2012-06, Vol.7 (6), p.e40168</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Janssen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://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>Janssen et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c809t-cf7b9427caf80664f107b535b8ce0aabc09663b75e7b81fe5c609467ded466773</citedby><cites>FETCH-LOGICAL-c809t-cf7b9427caf80664f107b535b8ce0aabc09663b75e7b81fe5c609467ded466773</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387020/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3387020/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23871,27929,27930,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22768248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Luque, Raul M.</contributor><creatorcontrib>Janssen, Sara</creatorcontrib><creatorcontrib>Laermans, Jorien</creatorcontrib><creatorcontrib>Iwakura, Hiroshi</creatorcontrib><creatorcontrib>Tack, Jan</creatorcontrib><creatorcontrib>Depoortere, Inge</creatorcontrib><title>Sensing of fatty acids for octanoylation of ghrelin involves a gustatory G-protein</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Ghrelin is an important regulator of energy--and glucose homeostasis. The octanoylation at Ser(3) is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell.
Wild-type (WT) and α-gustducin knockout (gust(-/-)) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo.
Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/-) mice. Gastric emptying was accelerated in WT but not in gust(-/-) mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels.
This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell.</description><subject>Agouti-Related Protein - genetics</subject><subject>Agouti-Related Protein - metabolism</subject><subject>alpha-Linolenic Acid - pharmacology</subject><subject>Animals</subject><subject>Biological effects</subject><subject>Biology</subject><subject>Body Weight - drug effects</subject><subject>Caprylates - administration & dosage</subject><subject>Caprylates - metabolism</subject><subject>Caprylates - pharmacology</subject><subject>Cell Line</subject><subject>Chains</subject><subject>Detection</subject><subject>Diet</subject><subject>Duodenum</subject><subject>Emptying</subject><subject>Fatty acids</subject><subject>Fatty Acids - metabolism</subject><subject>Feeding Behavior - drug effects</subject><subject>Fluorescent Antibody Technique</subject><subject>Food</subject><subject>Gastric emptying</subject><subject>Gene Expression Regulation - drug effects</subject><subject>Ghrelin</subject><subject>Ghrelin - metabolism</subject><subject>Gnat3 protein</subject><subject>Heterotrimeric GTP-Binding Proteins - metabolism</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Immunofluorescence</subject><subject>Linolenic acid</subject><subject>Linolenic acids</subject><subject>Lipids</subject><subject>Localization</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Motility</subject><subject>Octanoic acid</subject><subject>Oils & fats</subject><subject>Omega 3 fatty acids</subject><subject>Oral administration</subject><subject>Palmitic Acids - pharmacology</subject><subject>Peptides</subject><subject>Protein Transport - drug effects</subject><subject>Proteins</subject><subject>Receptors</subject><subject>Receptors, G-Protein-Coupled - metabolism</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>Rodents</subject><subject>Saturated fatty acids</subject><subject>siRNA</subject><subject>Stomach</subject><subject>Taste - 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The octanoylation at Ser(3) is essential for ghrelin's biological effects but the mechanisms involved in the octanoylation are unknown. We investigated whether the gustatory G-protein, α-gustducin, and the free fatty acid receptors GPR40 and GPR120 are involved in the fatty acid sensing mechanisms of the ghrelin cell.
Wild-type (WT) and α-gustducin knockout (gust(-/-)) mice were fed a glyceryl trioctanoate-enriched diet (OD) during 2 weeks. Ghrelin levels and gastric emptying were determined. Co-localization between GPR40, GPR120 and ghrelin or α-gustducin/α-transducin was investigated by immunofluorescence staining. The role of GPR120 in the effect of medium and long chain fatty acids on the release of ghrelin was studied in the ghrelinoma cell line, MGN3-1. The effect of the GPR40 agonist, MEDICA16, and the GPR120 agonist, grifolic acid, on ghrelin release was studied both in vitro and in vivo.
Feeding an OD specifically increased octanoyl ghrelin levels in the stomach of WT mice but not of gust(-/-) mice. Gastric emptying was accelerated in WT but not in gust(-/-) mice. GPR40 was colocalized with desoctanoyl but not with octanoyl ghrelin, α-gustducin or α-transducin positive cells in the stomach. GPR120 only colocalized with ghrelin in the duodenum. Addition of octanoic acid or α-linolenic acid to MGN3-1 cells increased and decreased octanoyl ghrelin levels, respectively. Both effects could not be blocked by GPR120 siRNA. MEDICA16 and grifolic acid did not affect ghrelin secretion in vitro but oral administration of grifolic acid increased plasma ghrelin levels.
This study provides the first evidence that α-gustducin is involved in the octanoylation of ghrelin and shows that the ghrelin cell can sense long- and medium-chain fatty acids directly. GPR120 but not GPR40 may play a role in the lipid sensing cascade of the ghrelin cell.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22768248</pmid><doi>10.1371/journal.pone.0040168</doi><tpages>e40168</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-06, Vol.7 (6), p.e40168 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1325045095 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Agouti-Related Protein - genetics Agouti-Related Protein - metabolism alpha-Linolenic Acid - pharmacology Animals Biological effects Biology Body Weight - drug effects Caprylates - administration & dosage Caprylates - metabolism Caprylates - pharmacology Cell Line Chains Detection Diet Duodenum Emptying Fatty acids Fatty Acids - metabolism Feeding Behavior - drug effects Fluorescent Antibody Technique Food Gastric emptying Gene Expression Regulation - drug effects Ghrelin Ghrelin - metabolism Gnat3 protein Heterotrimeric GTP-Binding Proteins - metabolism Homeostasis Humans Immunofluorescence Linolenic acid Linolenic acids Lipids Localization Male Medical research Medicine Mice Mice, Inbred C57BL Motility Octanoic acid Oils & fats Omega 3 fatty acids Oral administration Palmitic Acids - pharmacology Peptides Protein Transport - drug effects Proteins Receptors Receptors, G-Protein-Coupled - metabolism RNA, Messenger - genetics RNA, Messenger - metabolism Rodents Saturated fatty acids siRNA Stomach Taste - drug effects Transducin |
| title | Sensing of fatty acids for octanoylation of ghrelin involves a gustatory G-protein |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-14T06%3A49%3A02IST&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=Sensing%20of%20fatty%20acids%20for%20octanoylation%20of%20ghrelin%20involves%20a%20gustatory%20G-protein&rft.jtitle=PloS%20one&rft.au=Janssen,%20Sara&rft.date=2012-06-29&rft.volume=7&rft.issue=6&rft.spage=e40168&rft.pages=e40168-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0040168&rft_dat=%3Cgale_plos_%3EA477004491%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=1325045095&rft_id=info:pmid/22768248&rft_galeid=A477004491&rft_doaj_id=oai_doaj_org_article_8bceecfb42ef42ffbb55d627c48f9b13&rfr_iscdi=true |