Oral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice

Akihiro Uchida,1,&ast; Taro Yasuma,1,2,&ast; Atsuro Takeshita,1,2,&ast; Masaaki Toda,2 Yuko Okano,1,2 Kota Nishihama,1 Corina N D’Alessandro-Gabazza,2 Valeria Fridman D’Alessandro,2 Chisa Inoue,1 Takehiro Takagi,3 Hiroyuki Mukaiyama,4 Norio Takagi,4 Katsumi Shimizu,4 Yutaka Yano,1 Esteba...

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Autores principales:	Uchida A, Yasuma T, Takeshita A, Toda M, Okano Y, Nishihama K, D'Alessandro-Gabazza CN, Fridman D'Alessandro V, Inoue C, Takagi T, Mukaiyama H, Takagi N, Shimizu K, Yano Y, Gabazza EC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	insulin resistance limonite diabetes streptozotocin metabolic syndrome gut microbiome Pathology RB1-214 Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/25413cc3a98644ad8dcc3178adb57ac7
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spelling	oai:doaj.org-article:25413cc3a98644ad8dcc3178adb57ac72021-12-02T18:34:17ZOral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice1178-7031https://doaj.org/article/25413cc3a98644ad8dcc3178adb57ac72021-07-01T00:00:00Zhttps://www.dovepress.com/oral-limonite-supplement-ameliorates-glucose-intolerance-in-diabetic-a-peer-reviewed-fulltext-article-JIRhttps://doaj.org/toc/1178-7031Akihiro Uchida,1,&ast; Taro Yasuma,1,2,&ast; Atsuro Takeshita,1,2,&ast; Masaaki Toda,2 Yuko Okano,1,2 Kota Nishihama,1 Corina N D’Alessandro-Gabazza,2 Valeria Fridman D’Alessandro,2 Chisa Inoue,1 Takehiro Takagi,3 Hiroyuki Mukaiyama,4 Norio Takagi,4 Katsumi Shimizu,4 Yutaka Yano,1 Esteban C Gabazza2 1Department of Diabetes and Endocrinology, Mie University Faculty and Graduate School of Medicine, Tsu, Mie, Japan; 2Department of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, Mie, Japan; 3Iwasaki Hospital, Tsu, Mie, Japan; 4Tanisake Corporation, Gifu, Japan&ast;These authors contributed equally to this workCorrespondence: Esteban C GabazzaDepartment of Immunology, Mie University School of Medicine, Edobashi 2-174, Tsu-City, Mie, 514-8507, JapanTel +81 59 231 5037Fax +81 59 231 5225Email gabazza@doc.medic.mie-u.ac.jpIntroduction: Diabetes mellitus is a serious threat to public health worldwide. It causes a substantial economic burden, mental and physical disabilities, poor quality of life, and high mortality. Limonite is formed when iron-rich materials from the underground emerge and oxidized on the ground surface. It is currently used to purify contaminated water, absorption of irritant gases, and improve livestock breeding. Limonite can change the composition of environmental microbial communities. In the present study, we evaluated whether limonite can ameliorate glucose metabolism abnormalities by remodeling the gut microbiome.Methods: The investigation was performed using mouse models of streptozotocin-induced diabetes mellitus and high-calorie diet-induced metabolic syndrome.Results: Oral limonite supplement was associated with significant body weight recovery, reduced glycemia with improved insulin secretion, increased number of regulatory T cells, and abundant beneficial gut microbial populations in mice with diabetes mellitus compared to control. Similarly, mice with obesity fed with limonite supplements had significantly reduced body weight, insulin resistance, steatohepatitis, and systemic inflammatory response with significant gut microbiome remodeling.Conclusion: This study demonstrates that limonite supplement ameliorates abnormal glucose metabolism in diabetes mellitus and obesity. Gut microbiome remodeling, inhibition of inflammatory cytokines, and the host immune response regulation may explain the limonite’s beneficial activity under pathological conditions in vivo.Keywords: insulin resistance, limonite, diabetes, streptozotocin, metabolic syndrome, gut microbiomeUchida AYasuma TTakeshita AToda MOkano YNishihama KD'Alessandro-Gabazza CNFridman D'Alessandro VInoue CTakagi TMukaiyama HTakagi NShimizu KYano YGabazza ECDove Medical Pressarticleinsulin resistancelimonitediabetesstreptozotocinmetabolic syndromegut microbiomePathologyRB1-214Therapeutics. PharmacologyRM1-950ENJournal of Inflammation Research, Vol Volume 14, Pp 3089-3105 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	insulin resistance limonite diabetes streptozotocin metabolic syndrome gut microbiome Pathology RB1-214 Therapeutics. Pharmacology RM1-950
spellingShingle	insulin resistance limonite diabetes streptozotocin metabolic syndrome gut microbiome Pathology RB1-214 Therapeutics. Pharmacology RM1-950 Uchida A Yasuma T Takeshita A Toda M Okano Y Nishihama K D'Alessandro-Gabazza CN Fridman D'Alessandro V Inoue C Takagi T Mukaiyama H Takagi N Shimizu K Yano Y Gabazza EC Oral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice
description	Akihiro Uchida,1,&ast; Taro Yasuma,1,2,&ast; Atsuro Takeshita,1,2,&ast; Masaaki Toda,2 Yuko Okano,1,2 Kota Nishihama,1 Corina N D’Alessandro-Gabazza,2 Valeria Fridman D’Alessandro,2 Chisa Inoue,1 Takehiro Takagi,3 Hiroyuki Mukaiyama,4 Norio Takagi,4 Katsumi Shimizu,4 Yutaka Yano,1 Esteban C Gabazza2 1Department of Diabetes and Endocrinology, Mie University Faculty and Graduate School of Medicine, Tsu, Mie, Japan; 2Department of Immunology, Mie University Faculty and Graduate School of Medicine, Tsu, Mie, Japan; 3Iwasaki Hospital, Tsu, Mie, Japan; 4Tanisake Corporation, Gifu, Japan&ast;These authors contributed equally to this workCorrespondence: Esteban C GabazzaDepartment of Immunology, Mie University School of Medicine, Edobashi 2-174, Tsu-City, Mie, 514-8507, JapanTel +81 59 231 5037Fax +81 59 231 5225Email gabazza@doc.medic.mie-u.ac.jpIntroduction: Diabetes mellitus is a serious threat to public health worldwide. It causes a substantial economic burden, mental and physical disabilities, poor quality of life, and high mortality. Limonite is formed when iron-rich materials from the underground emerge and oxidized on the ground surface. It is currently used to purify contaminated water, absorption of irritant gases, and improve livestock breeding. Limonite can change the composition of environmental microbial communities. In the present study, we evaluated whether limonite can ameliorate glucose metabolism abnormalities by remodeling the gut microbiome.Methods: The investigation was performed using mouse models of streptozotocin-induced diabetes mellitus and high-calorie diet-induced metabolic syndrome.Results: Oral limonite supplement was associated with significant body weight recovery, reduced glycemia with improved insulin secretion, increased number of regulatory T cells, and abundant beneficial gut microbial populations in mice with diabetes mellitus compared to control. Similarly, mice with obesity fed with limonite supplements had significantly reduced body weight, insulin resistance, steatohepatitis, and systemic inflammatory response with significant gut microbiome remodeling.Conclusion: This study demonstrates that limonite supplement ameliorates abnormal glucose metabolism in diabetes mellitus and obesity. Gut microbiome remodeling, inhibition of inflammatory cytokines, and the host immune response regulation may explain the limonite’s beneficial activity under pathological conditions in vivo.Keywords: insulin resistance, limonite, diabetes, streptozotocin, metabolic syndrome, gut microbiome
format	article
author	Uchida A Yasuma T Takeshita A Toda M Okano Y Nishihama K D'Alessandro-Gabazza CN Fridman D'Alessandro V Inoue C Takagi T Mukaiyama H Takagi N Shimizu K Yano Y Gabazza EC
author_facet	Uchida A Yasuma T Takeshita A Toda M Okano Y Nishihama K D'Alessandro-Gabazza CN Fridman D'Alessandro V Inoue C Takagi T Mukaiyama H Takagi N Shimizu K Yano Y Gabazza EC
author_sort	Uchida A
title	Oral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice
title_short	Oral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice
title_full	Oral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice
title_fullStr	Oral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice
title_full_unstemmed	Oral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice
title_sort	oral limonite supplement ameliorates glucose intolerance in diabetic and obese mice
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/25413cc3a98644ad8dcc3178adb57ac7
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Oral Limonite Supplement Ameliorates Glucose Intolerance in Diabetic and Obese Mice

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