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Influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice
Plasma xanthine oxidoreductase (XOR) activity is high in metabolic disorders such as diabetic mellitus, obesity, or overweight. Thus, this study investigated whether the XOR inhibitor, topiroxostat, affected body weight. Male db/db mice were fed standard diets with or without topiroxostat for 4 week...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044114/ https://www.ncbi.nlm.nih.gov/pubmed/33850106 http://dx.doi.org/10.1038/s41387-021-00155-2 |
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author | Nakamura, Takashi Nampei, Mai Murase, Takayo Satoh, Etsuko Akari, Seigo Katoh, Noriaki Mizukami, Hiroki |
author_facet | Nakamura, Takashi Nampei, Mai Murase, Takayo Satoh, Etsuko Akari, Seigo Katoh, Noriaki Mizukami, Hiroki |
author_sort | Nakamura, Takashi |
collection | PubMed |
description | Plasma xanthine oxidoreductase (XOR) activity is high in metabolic disorders such as diabetic mellitus, obesity, or overweight. Thus, this study investigated whether the XOR inhibitor, topiroxostat, affected body weight. Male db/db mice were fed standard diets with or without topiroxostat for 4 weeks. Body weight and food intake were constantly monitored, along with monitoring plasma biochemical markers, including insulin and XOR activity. Additionally, hepatic hypoxanthine and XOR activity were also documented. Single regression analysis was performed to determine the mechanism. Topiroxostat treatment suppressed weight gain relative to the vehicle without any impact on food intake. However, the weight of fat pads and hepatic and muscle triglyceride content did not change. Topiroxostat decreased the plasma uric acid and increased hepatic hypoxanthine in response to the inhibition of XOR activity. Plasma ketone body and free fatty acid were also increased. Moreover, fat weight was weakly associated with plasma XOR activity in the diabetic state and was negatively associated with ketone body by topiroxostat. These results suggested that topiroxostat amplified the burning of lipids and the salvage pathway, resulting in predisposing the body toward catabolism. The inhibition of plasma XOR activity may contribute to weight loss. |
format | Online Article Text |
id | pubmed-8044114 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-80441142021-04-28 Influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice Nakamura, Takashi Nampei, Mai Murase, Takayo Satoh, Etsuko Akari, Seigo Katoh, Noriaki Mizukami, Hiroki Nutr Diabetes Brief Communication Plasma xanthine oxidoreductase (XOR) activity is high in metabolic disorders such as diabetic mellitus, obesity, or overweight. Thus, this study investigated whether the XOR inhibitor, topiroxostat, affected body weight. Male db/db mice were fed standard diets with or without topiroxostat for 4 weeks. Body weight and food intake were constantly monitored, along with monitoring plasma biochemical markers, including insulin and XOR activity. Additionally, hepatic hypoxanthine and XOR activity were also documented. Single regression analysis was performed to determine the mechanism. Topiroxostat treatment suppressed weight gain relative to the vehicle without any impact on food intake. However, the weight of fat pads and hepatic and muscle triglyceride content did not change. Topiroxostat decreased the plasma uric acid and increased hepatic hypoxanthine in response to the inhibition of XOR activity. Plasma ketone body and free fatty acid were also increased. Moreover, fat weight was weakly associated with plasma XOR activity in the diabetic state and was negatively associated with ketone body by topiroxostat. These results suggested that topiroxostat amplified the burning of lipids and the salvage pathway, resulting in predisposing the body toward catabolism. The inhibition of plasma XOR activity may contribute to weight loss. Nature Publishing Group UK 2021-04-13 /pmc/articles/PMC8044114/ /pubmed/33850106 http://dx.doi.org/10.1038/s41387-021-00155-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Brief Communication Nakamura, Takashi Nampei, Mai Murase, Takayo Satoh, Etsuko Akari, Seigo Katoh, Noriaki Mizukami, Hiroki Influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice |
title | Influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice |
title_full | Influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice |
title_fullStr | Influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice |
title_full_unstemmed | Influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice |
title_short | Influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice |
title_sort | influence of xanthine oxidoreductase inhibitor, topiroxostat, on body weight of diabetic obese mice |
topic | Brief Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044114/ https://www.ncbi.nlm.nih.gov/pubmed/33850106 http://dx.doi.org/10.1038/s41387-021-00155-2 |
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