Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism

Satoko Kawarasaki,1 Honami Sawazaki,1 Hiroaki Iijima,2 Su-Ping Ng,1 Jungin Kwon,1 Shinsuke Mohri,1 Mari Iwase,1 Huei-Fen Jheng,1 Haruya Takahashi,1 Wataru Nomura,1,3 Kazuo Inoue,1,3 Teruo Kawada,1,3 Tsuyoshi Goto1,3 1Laboratory of Molecular Function of Food, Division of Food Science and Biotechnolog...

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Autores principales:	Kawarasaki S, Sawazaki H, Iijima H, Ng SP, Kwon J, Mohri S, Iwase M, Jheng HF, Takahashi H, Nomura W, Inoue K, Kawada T, Goto T
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	sglt2 inhibitor obesity dosing method Specialties of internal medicine RC581-951
Acceso en línea:	https://doaj.org/article/7c7818dc5d014128b75a709829e50aa7
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spelling	oai:doaj.org-article:7c7818dc5d014128b75a709829e50aa72021-12-02T13:38:35ZComparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism1178-7007https://doaj.org/article/7c7818dc5d014128b75a709829e50aa72020-11-01T00:00:00Zhttps://www.dovepress.com/comparative-analysis-of-the-preventive-effects-of-canagliflozin-a-sodi-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Satoko Kawarasaki,1 Honami Sawazaki,1 Hiroaki Iijima,2 Su-Ping Ng,1 Jungin Kwon,1 Shinsuke Mohri,1 Mari Iwase,1 Huei-Fen Jheng,1 Haruya Takahashi,1 Wataru Nomura,1,3 Kazuo Inoue,1,3 Teruo Kawada,1,3 Tsuyoshi Goto1,3 1Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011, Japan; 2Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan; 3Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8317, JapanCorrespondence: Tsuyoshi GotoLaboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011, JapanTel +81-774-38-3753Fax +81-774-38-3752Email goto.tsuyoshi.6x@kyoto-u.ac.jpPurpose: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have various pleiotropic effects, including body weight reduction, and therefore have the potential to be used in various applications. However, such effects have not been fully investigated; thus, non-clinical studies using animal models are needed. In animal experiments, SGLT2 inhibitors are usually administered by oral or dietary methods. However, the detailed characteristics of these dosing methods, especially to induce their pleiotropic effects, have not been reported. Therefore, we compared the preventive effects of canagliflozin, an SGLT2 inhibitor, on body weight gain following oral gavage and dietary administration methods in a mouse model of diet-induced obesity.Methods: Canagliflozin was dosed by oral gavage or dietary administration for 9 weeks to 6-week-old C57BL/6N mice fed a high-fat diet, and parameters related to obesity were evaluated.Results: The suppression of body weight gain, fat mass, and hepatic lipid content was observed following both dosing methods, whereas the effect on body weight tended to be stronger in the dietary administration group. In adipose tissue, fatty acid synthase expression was significantly decreased in the dietary administration group, and its expression was significantly correlated with fat mass. However, the expression of genes related to fatty acid oxidation was unchanged, indicating that the preventive effect on body weight gain was mediated mainly through the suppression of lipid synthesis rather than the promotion of lipid oxidation.Conclusion: Canagliflozin prevented body weight gain through the suppression of lipid synthesis via both dosing methods, although there were some differences in the efficacy. The findings of our study can help to identify new mechanisms of action of SGLT2 inhibitors and potential applications.Keywords: SGLT2 inhibitor, obesity, dosing methodKawarasaki SSawazaki HIijima HNg SPKwon JMohri SIwase MJheng HFTakahashi HNomura WInoue KKawada TGoto TDove Medical Pressarticlesglt2 inhibitorobesitydosing methodSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 13, Pp 4353-4359 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	sglt2 inhibitor obesity dosing method Specialties of internal medicine RC581-951
spellingShingle	sglt2 inhibitor obesity dosing method Specialties of internal medicine RC581-951 Kawarasaki S Sawazaki H Iijima H Ng SP Kwon J Mohri S Iwase M Jheng HF Takahashi H Nomura W Inoue K Kawada T Goto T Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism
description	Satoko Kawarasaki,1 Honami Sawazaki,1 Hiroaki Iijima,2 Su-Ping Ng,1 Jungin Kwon,1 Shinsuke Mohri,1 Mari Iwase,1 Huei-Fen Jheng,1 Haruya Takahashi,1 Wataru Nomura,1,3 Kazuo Inoue,1,3 Teruo Kawada,1,3 Tsuyoshi Goto1,3 1Laboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011, Japan; 2Ikuyaku. Integrated Value Development Division, Mitsubishi Tanabe Pharma Corporation, Tokyo, Japan; 3Research Unit for Physiological Chemistry, The Center for the Promotion of Interdisciplinary Education and Research, Kyoto University, Kyoto 606-8317, JapanCorrespondence: Tsuyoshi GotoLaboratory of Molecular Function of Food, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Uji 611-0011, JapanTel +81-774-38-3753Fax +81-774-38-3752Email goto.tsuyoshi.6x@kyoto-u.ac.jpPurpose: Sodium-glucose co-transporter-2 (SGLT2) inhibitors have various pleiotropic effects, including body weight reduction, and therefore have the potential to be used in various applications. However, such effects have not been fully investigated; thus, non-clinical studies using animal models are needed. In animal experiments, SGLT2 inhibitors are usually administered by oral or dietary methods. However, the detailed characteristics of these dosing methods, especially to induce their pleiotropic effects, have not been reported. Therefore, we compared the preventive effects of canagliflozin, an SGLT2 inhibitor, on body weight gain following oral gavage and dietary administration methods in a mouse model of diet-induced obesity.Methods: Canagliflozin was dosed by oral gavage or dietary administration for 9 weeks to 6-week-old C57BL/6N mice fed a high-fat diet, and parameters related to obesity were evaluated.Results: The suppression of body weight gain, fat mass, and hepatic lipid content was observed following both dosing methods, whereas the effect on body weight tended to be stronger in the dietary administration group. In adipose tissue, fatty acid synthase expression was significantly decreased in the dietary administration group, and its expression was significantly correlated with fat mass. However, the expression of genes related to fatty acid oxidation was unchanged, indicating that the preventive effect on body weight gain was mediated mainly through the suppression of lipid synthesis rather than the promotion of lipid oxidation.Conclusion: Canagliflozin prevented body weight gain through the suppression of lipid synthesis via both dosing methods, although there were some differences in the efficacy. The findings of our study can help to identify new mechanisms of action of SGLT2 inhibitors and potential applications.Keywords: SGLT2 inhibitor, obesity, dosing method
format	article
author	Kawarasaki S Sawazaki H Iijima H Ng SP Kwon J Mohri S Iwase M Jheng HF Takahashi H Nomura W Inoue K Kawada T Goto T
author_facet	Kawarasaki S Sawazaki H Iijima H Ng SP Kwon J Mohri S Iwase M Jheng HF Takahashi H Nomura W Inoue K Kawada T Goto T
author_sort	Kawarasaki S
title	Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism
title_short	Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism
title_full	Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism
title_fullStr	Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism
title_full_unstemmed	Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism
title_sort	comparative analysis of the preventive effects of canagliflozin, a sodium-glucose co-transporter-2 inhibitor, on body weight gain between oral gavage and dietary administration by focusing on fatty acid metabolism
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/7c7818dc5d014128b75a709829e50aa7
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Comparative Analysis of the Preventive Effects of Canagliflozin, a Sodium-Glucose Co-Transporter-2 Inhibitor, on Body Weight Gain Between Oral Gavage and Dietary Administration by Focusing on Fatty Acid Metabolism

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