| Activation of ectopic olfactory receptor 544 induces GLP-1 secretion and regulates gut inflammation | |
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| 년도 | 2021 |
| 날짜 | Dec |
| 페이지 / 학회지명 |
13(1):1987782 / Gut Microbes |
| 논문저자 | Chunyan Wu 1, Mi-Young Jeong 1, Jung Yeon Kim 1, Giljae Lee 2 3, Ji-Sun Kim 1, Yu Eun Cheong 1, Hyena Kang 2 3, Chung Hwan Cho 2 3, Jimin Kim 1, Min Kyung Park 4, You Kyoung Shin 5, Kyoung Heon Kim 1, Geun Hee Seol 5, Seung Hoi Koo 6, GwangPyo Ko 2 3, Sun |
| Link |
https://www.tandfonline.com/doi/full/10.1080/19490976.2021.1987782
244회 연결
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1 Department of Biotechnology, School of Life Science and Biotechnology for BK21 Plus, Korea University, Seoul, Republic of Korea. 2 Department of Environmental Health Sciences, Seoul National University, Seoul, Republic of Korea. 3 Center for Human and Environmental Microbiome, Seoul National University, Seoul, Republic of Korea. 4 Department of Food Science and Engineering, Ewha Womans University, Seoul, Republic of Korea. 5 Department of Basic Nursing Science, School of Nursing, Korea University, Seoul, Republic of Korea. 6 Division of Biological Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea. 7 Department of Food Bioscience and Technology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea. Abstract 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 mice fed a HFD and orally administered AzA, GLP-1 plasma levels were elevated in mice. 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. Keywords: GLP-1; Olfr544; colonic inflammation; ectopic olfactory receptor; gut microbiome; metabolome. |
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