Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet‐induced obese mice
Abstract Aims/Introduction The mechanisms underlying the effect of sodium‐glucose cotransporter 2 (SGLT2) inhibitors on aortic endothelial dysfunction in diet‐induced obesity are not clearly understood. This study investigated whether SGLT2 inhibition by luseogliflozin improved free fatty acid (FFA)...
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| Format: | Article |
| Language: | English |
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Wiley
2023-04-01
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| Series: | Journal of Diabetes Investigation |
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| Online Access: | https://doi.org/10.1111/jdi.13981 |
| _version_ | 1797861898233839616 |
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| author | Shigeru Kawade Kazuma Ogiso Sigfrid Casmir Shayo Takahiko Obo Aiko Arimura Hiroshi Hashiguchi Takahisa Deguchi Yoshihiko Nishio |
| author_facet | Shigeru Kawade Kazuma Ogiso Sigfrid Casmir Shayo Takahiko Obo Aiko Arimura Hiroshi Hashiguchi Takahisa Deguchi Yoshihiko Nishio |
| author_sort | Shigeru Kawade |
| collection | DOAJ |
| description | Abstract Aims/Introduction The mechanisms underlying the effect of sodium‐glucose cotransporter 2 (SGLT2) inhibitors on aortic endothelial dysfunction in diet‐induced obesity are not clearly understood. This study investigated whether SGLT2 inhibition by luseogliflozin improved free fatty acid (FFA)‐induced endothelial dysfunction in high‐fat diet (HFD)‐induced obese mice. Materials and Methods Mice were fed a control diet or high‐fat diet for 8 weeks, and then each diet with or without luseogliflozin was provided for an additional 8 weeks under free or paired feeding. Afterward, the thoracic aortas were removed and utilized for the experiments. Results Luseogliflozin treatment decreased body weight, fasting blood glucose, insulin, and total cholesterol in HFD‐fed mice only under paired feeding but not under free feeding. Endothelial‐dependent vasodilation under FFA exposure conditions was significantly lower in HFD‐fed mice than in control diet‐fed mice, and luseogliflozin treatment ameliorated FFA‐induced endothelial dysfunction. Reactive oxygen species (ROS) production induced by FFA was significantly increased in HFD‐induced obese mice. Luseogliflozin treatment increased the expression of superoxide dismutase 2 (SOD2), an antioxidative molecule, and reduced FFA‐induced ROS production in the thoracic aorta. Superoxide dismutase reversed FFA‐induced endothelial dysfunction in HFD‐fed mice. Conclusions It was shown that caloric restriction is important for the effect of luseogliflozin on metabolic parameters and endothelial dysfunction. Furthermore, SGLT2 inhibition by luseogliflozin possibly ameliorates FFA‐induced endothelial dysfunction by increasing SOD2 expression and decreasing reactive oxygen species production in the thoracic aorta. |
| first_indexed | 2024-04-09T22:11:49Z |
| format | Article |
| id | doaj.art-796a01f6417b45e78836b6bebf0d6349 |
| institution | Directory Open Access Journal |
| issn | 2040-1116 2040-1124 |
| language | English |
| last_indexed | 2024-04-09T22:11:49Z |
| publishDate | 2023-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Investigation |
| spelling | doaj.art-796a01f6417b45e78836b6bebf0d63492023-03-23T10:50:45ZengWileyJournal of Diabetes Investigation2040-11162040-11242023-04-0114454855910.1111/jdi.13981Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet‐induced obese miceShigeru Kawade0Kazuma Ogiso1Sigfrid Casmir Shayo2Takahiko Obo3Aiko Arimura4Hiroshi Hashiguchi5Takahisa Deguchi6Yoshihiko Nishio7Department of Diabetes and Endocrine Medicine Kagoshima University Graduate School of Medicine and Dental Sciences Kagoshima JapanDepartment of Diabetes and Endocrine Medicine Kagoshima University Graduate School of Medicine and Dental Sciences Kagoshima JapanDepartment of Diabetes and Endocrine Medicine Kagoshima University Graduate School of Medicine and Dental Sciences Kagoshima JapanDepartment of Diabetes and Endocrine Medicine Kagoshima University Graduate School of Medicine and Dental Sciences Kagoshima JapanDepartment of Diabetes and Endocrine Medicine Kagoshima University Graduate School of Medicine and Dental Sciences Kagoshima JapanDepartment of Diabetes and Endocrine Medicine Kagoshima University Graduate School of Medicine and Dental Sciences Kagoshima JapanDepartment of Diabetes and Endocrine Medicine Kagoshima University Graduate School of Medicine and Dental Sciences Kagoshima JapanDepartment of Diabetes and Endocrine Medicine Kagoshima University Graduate School of Medicine and Dental Sciences Kagoshima JapanAbstract Aims/Introduction The mechanisms underlying the effect of sodium‐glucose cotransporter 2 (SGLT2) inhibitors on aortic endothelial dysfunction in diet‐induced obesity are not clearly understood. This study investigated whether SGLT2 inhibition by luseogliflozin improved free fatty acid (FFA)‐induced endothelial dysfunction in high‐fat diet (HFD)‐induced obese mice. Materials and Methods Mice were fed a control diet or high‐fat diet for 8 weeks, and then each diet with or without luseogliflozin was provided for an additional 8 weeks under free or paired feeding. Afterward, the thoracic aortas were removed and utilized for the experiments. Results Luseogliflozin treatment decreased body weight, fasting blood glucose, insulin, and total cholesterol in HFD‐fed mice only under paired feeding but not under free feeding. Endothelial‐dependent vasodilation under FFA exposure conditions was significantly lower in HFD‐fed mice than in control diet‐fed mice, and luseogliflozin treatment ameliorated FFA‐induced endothelial dysfunction. Reactive oxygen species (ROS) production induced by FFA was significantly increased in HFD‐induced obese mice. Luseogliflozin treatment increased the expression of superoxide dismutase 2 (SOD2), an antioxidative molecule, and reduced FFA‐induced ROS production in the thoracic aorta. Superoxide dismutase reversed FFA‐induced endothelial dysfunction in HFD‐fed mice. Conclusions It was shown that caloric restriction is important for the effect of luseogliflozin on metabolic parameters and endothelial dysfunction. Furthermore, SGLT2 inhibition by luseogliflozin possibly ameliorates FFA‐induced endothelial dysfunction by increasing SOD2 expression and decreasing reactive oxygen species production in the thoracic aorta.https://doi.org/10.1111/jdi.13981Aortic endothelial dysfunctionOxidative stressSodium‐glucose cotransporter 2 |
| spellingShingle | Shigeru Kawade Kazuma Ogiso Sigfrid Casmir Shayo Takahiko Obo Aiko Arimura Hiroshi Hashiguchi Takahisa Deguchi Yoshihiko Nishio Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet‐induced obese mice Journal of Diabetes Investigation Aortic endothelial dysfunction Oxidative stress Sodium‐glucose cotransporter 2 |
| title | Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet‐induced obese mice |
| title_full | Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet‐induced obese mice |
| title_fullStr | Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet‐induced obese mice |
| title_full_unstemmed | Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet‐induced obese mice |
| title_short | Luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression, promote antioxidative effects, and attenuate aortic endothelial dysfunction in diet‐induced obese mice |
| title_sort | luseogliflozin and caloric intake restriction increase superoxide dismutase 2 expression promote antioxidative effects and attenuate aortic endothelial dysfunction in diet induced obese mice |
| topic | Aortic endothelial dysfunction Oxidative stress Sodium‐glucose cotransporter 2 |
| url | https://doi.org/10.1111/jdi.13981 |
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