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An olive-derived elenolic acid stimulates hormone release from L-cells and exerts potent beneficial metabolic effects in obese diabetic mice

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dc.contributor.authorWang, Yaoen
dc.contributor.authorWu, Yajunen
dc.contributor.authorWang, Aipingen
dc.contributor.authorWang, Aihuaen
dc.contributor.authorAlkhalidy, Hanaen
dc.contributor.authorHelm, Richarden
dc.contributor.authorZhang, Shijunen
dc.contributor.authorMa, Hongguangen
dc.contributor.authorZhang, Yanen
dc.contributor.authorGilbert, Elizabeth R.en
dc.contributor.authorXu, Binen
dc.contributor.authorLiu, Dongminen
dc.date.accessioned2023-02-07T18:31:15Zen
dc.date.available2023-02-07T18:31:15Zen
dc.date.issued2022-11-01en
dc.date.updated2023-02-07T14:48:45Zen
dc.description.abstractInsulin resistance and progressive decline in functional β-cell mass are two key factors for developing type 2 diabetes (T2D), which is largely driven by overweight and obesity, a significant obstacle for effective metabolic control in many patients with T2D. Thus, agents that simultaneously ameliorate obesity and act on multiple pathophysiological components could be more effective for treating T2D. Here, we report that elenolic acid (EA), a phytochemical, is such a dual-action agent. we show that EA dose-dependently stimulates GLP-1 secretion in mouse clonal L-cells and isolated mouse ileum crypts. In addition, EA induces L-cells to secrete peptide YY (PYY). EA induces a rapid increase in intracellular [Ca2+]i and the production of inositol trisphosphate in L-cells, indicating that EA activates phospholipase C (PLC)-mediated signaling. Consistently, inhibition of (PLC) or Gαq ablates EA-stimulated increase of [Ca2+]i and GLP-1 secretion. In vivo, a single dose of EA acutely stimulates GLP-1 and PYY secretion in mice, accompanied with an improved glucose tolerance and insulin levels. Oral administration of EA at a dose of 50 mg/kg/day for 2 weeks normalized the fasting blood glucose and restored glucose tolerance in high-fat diet-induced obese (DIO) mice to levels that were comparable to chow-fed mice. In addition, EA suppresses appetite, reduces food intake, promotes weight loss, and reverses perturbated metabolic variables in obese mice. These results suggest that EA could be a dual-action agent as an alternative or adjuvant treatment for both T2D and obesity.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fnut.2022.1051452en
dc.identifier.eissn2296-861Xen
dc.identifier.issn2296-861Xen
dc.identifier.orcidGilbert, Elizabeth [0000-0003-4541-9414]en
dc.identifier.orcidHelm, Richard [0000-0001-5317-0925]en
dc.identifier.orcidLiu, Dongmin [0000-0002-3877-8198]en
dc.identifier.otherPMC9664001en
dc.identifier.pmid36386896en
dc.identifier.urihttp://hdl.handle.net/10919/113704en
dc.identifier.volume9en
dc.language.isoenen
dc.publisherFrontiersen
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pubmed/36386896en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectelenolic aciden
dc.subjectglucagon-like peptide-1en
dc.subjectmiceen
dc.subjectobesityen
dc.subjectpeptide YYen
dc.subjecttype 2 diabetesen
dc.subjectNutritionen
dc.subjectComplementary and Integrative Healthen
dc.subjectPreventionen
dc.subjectDiabetesen
dc.subject5 Development of treatments and therapeutic interventionsen
dc.subject5.1 Pharmaceuticalsen
dc.subjectMetabolic and endocrineen
dc.subjectCanceren
dc.titleAn olive-derived elenolic acid stimulates hormone release from L-cells and exerts potent beneficial metabolic effects in obese diabetic miceen
dc.title.serialFrontiers in Nutritionen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherJournal Articleen
dcterms.dateAccepted2022-10-11en
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Human Nutrition, Foods, & Exerciseen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/School of Plant and Environmental Sciencesen

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