Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation

Olfactory receptors are ectopically expressed in extra-nasal tissues. The gut is constantly exposed to high levels of odorants where ectopic olfactory receptors may play critical roles. Activation of ectopic olfactory receptor 544 (Olfr544) by azelaic acid (AzA), an Olfr544 ligand, reduces adiposity...

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Autores principales:	Chunyan Wu, Mi-Young Jeong, Jung Yeon Kim, Giljae Lee, Ji-Sun Kim, Yu Eun Cheong, Hyena Kang, Chung Hwan Cho, Jimin Kim, Min Kyung Park, You Kyoung Shin, Kyoung Heon Kim, Geun Hee Seol, Seung Hoi Koo, GwangPyo Ko, Sung-Joon Lee
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2021
Materias:	olfr544 ectopic olfactory receptor glp-1 gut microbiome metabolome colonic inflammation Diseases of the digestive system. Gastroenterology RC799-869
Acceso en línea:	https://doaj.org/article/db55a877eea0458bbe368e938b3c7ecc
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spelling	oai:doaj.org-article:db55a877eea0458bbe368e938b3c7ecc2021-11-26T11:19:48ZActivation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation1949-09761949-098410.1080/19490976.2021.1987782https://doaj.org/article/db55a877eea0458bbe368e938b3c7ecc2021-01-01T00:00:00Zhttp://dx.doi.org/10.1080/19490976.2021.1987782https://doaj.org/toc/1949-0976https://doaj.org/toc/1949-0984Olfactory receptors are ectopically expressed in extra-nasal tissues. The gut is constantly exposed to high levels of odorants where ectopic olfactory receptors may play critical roles. Activation of ectopic olfactory receptor 544 (Olfr544) by azelaic acid (AzA), an Olfr544 ligand, reduces adiposity in mice fed a high-fat diet (HFD) by regulating fuel preference to fats. Herein, we investigated the novel function of Olfr544 in the gut. In GLUTag cells, AzA induces the cAMP-PKA-CREB signaling axis and increases the secretion of GLP-1, an enteroendocrine hormone with anti-obesity effects. In wild-type (WT) mice injected AzA, GLP-1 plasma levels were elevated. The induction of GLP-1 secretion was negated in cells with Olfr544 gene knockdown and in Olfr544-deficient mice. Gut microbiome analysis revealed that AzA increased the levels of Bacteroides acidifaciens and microbiota associated with antioxidant pathways. In fecal metabolomics analysis, the levels of succinate and trehalose, metabolites correlated with a lean phenotype, were elevated by AzA. The function of Olfr544 in gut inflammation, a key feature in obesity, was further investigated. In RNA sequencing analysis, AzA suppressed LPS-induced activation of inflammatory pathways and reduced TNF-α and IL-6 expression, thereby improving intestinal permeability. The effects of AzA on the gut metabolome, microbiome, and colon inflammation were abrogated in Olfr544-KO mice. These results collectively demonstrated that activation of Olfr544 by AzA in the gut exerts multiple effects by regulating GLP-1 secretion, gut microbiome and metabolites, and colonic inflammation in anti-obesogenic phenotypes and, thus, may be applied for obesity therapeutics.Chunyan WuMi-Young JeongJung Yeon KimGiljae LeeJi-Sun KimYu Eun CheongHyena KangChung Hwan ChoJimin KimMin Kyung ParkYou Kyoung ShinKyoung Heon KimGeun Hee SeolSeung Hoi KooGwangPyo KoSung-Joon LeeTaylor & Francis Grouparticleolfr544ectopic olfactory receptorglp-1gut microbiomemetabolomecolonic inflammationDiseases of the digestive system. GastroenterologyRC799-869ENGut Microbes, Vol 13, Iss 1 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	olfr544 ectopic olfactory receptor glp-1 gut microbiome metabolome colonic inflammation Diseases of the digestive system. Gastroenterology RC799-869
spellingShingle	olfr544 ectopic olfactory receptor glp-1 gut microbiome metabolome colonic inflammation Diseases of the digestive system. Gastroenterology RC799-869 Chunyan Wu Mi-Young Jeong Jung Yeon Kim Giljae Lee Ji-Sun Kim Yu Eun Cheong Hyena Kang Chung Hwan Cho Jimin Kim Min Kyung Park You Kyoung Shin Kyoung Heon Kim Geun Hee Seol Seung Hoi Koo GwangPyo Ko Sung-Joon Lee Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation
description	Olfactory receptors are ectopically expressed in extra-nasal tissues. The gut is constantly exposed to high levels of odorants where ectopic olfactory receptors may play critical roles. Activation of ectopic olfactory receptor 544 (Olfr544) by azelaic acid (AzA), an Olfr544 ligand, reduces adiposity in mice fed a high-fat diet (HFD) by regulating fuel preference to fats. Herein, we investigated the novel function of Olfr544 in the gut. In GLUTag cells, AzA induces the cAMP-PKA-CREB signaling axis and increases the secretion of GLP-1, an enteroendocrine hormone with anti-obesity effects. In wild-type (WT) mice injected AzA, GLP-1 plasma levels were elevated. The induction of GLP-1 secretion was negated in cells with Olfr544 gene knockdown and in Olfr544-deficient mice. Gut microbiome analysis revealed that AzA increased the levels of Bacteroides acidifaciens and microbiota associated with antioxidant pathways. In fecal metabolomics analysis, the levels of succinate and trehalose, metabolites correlated with a lean phenotype, were elevated by AzA. The function of Olfr544 in gut inflammation, a key feature in obesity, was further investigated. In RNA sequencing analysis, AzA suppressed LPS-induced activation of inflammatory pathways and reduced TNF-α and IL-6 expression, thereby improving intestinal permeability. The effects of AzA on the gut metabolome, microbiome, and colon inflammation were abrogated in Olfr544-KO mice. These results collectively demonstrated that activation of Olfr544 by AzA in the gut exerts multiple effects by regulating GLP-1 secretion, gut microbiome and metabolites, and colonic inflammation in anti-obesogenic phenotypes and, thus, may be applied for obesity therapeutics.
format	article
author	Chunyan Wu Mi-Young Jeong Jung Yeon Kim Giljae Lee Ji-Sun Kim Yu Eun Cheong Hyena Kang Chung Hwan Cho Jimin Kim Min Kyung Park You Kyoung Shin Kyoung Heon Kim Geun Hee Seol Seung Hoi Koo GwangPyo Ko Sung-Joon Lee
author_facet	Chunyan Wu Mi-Young Jeong Jung Yeon Kim Giljae Lee Ji-Sun Kim Yu Eun Cheong Hyena Kang Chung Hwan Cho Jimin Kim Min Kyung Park You Kyoung Shin Kyoung Heon Kim Geun Hee Seol Seung Hoi Koo GwangPyo Ko Sung-Joon Lee
author_sort	Chunyan Wu
title	Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation
title_short	Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation
title_full	Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation
title_fullStr	Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation
title_full_unstemmed	Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation
title_sort	activation of ectopic olfactory receptor 544 induces glp-1 secretion and regulates gut inflammation
publisher	Taylor & Francis Group
publishDate	2021
url	https://doaj.org/article/db55a877eea0458bbe368e938b3c7ecc
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Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation

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