The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese mice
Abstract Aims To investigate the influence of the dose in the FITC-Dextran 4kDa (FD-4) permeability test in an obese mouse model, we tested the bodyweight dose regimen and a lean body mass-based dose regimen in high fat diet (HFD) mice and low fat diet (LFD) mice. We hypothesized that the FD-4 perme...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-01-01
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| Series: | Nutrition & Diabetes |
| Online Access: | https://doi.org/10.1038/s41387-022-00230-2 |
| _version_ | 1797958421464481792 |
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| author | Louise M. Voetmann Bidda Rolin Rikke K. Kirk Charles Pyke Axel K. Hansen |
| author_facet | Louise M. Voetmann Bidda Rolin Rikke K. Kirk Charles Pyke Axel K. Hansen |
| author_sort | Louise M. Voetmann |
| collection | DOAJ |
| description | Abstract Aims To investigate the influence of the dose in the FITC-Dextran 4kDa (FD-4) permeability test in an obese mouse model, we tested the bodyweight dose regimen and a lean body mass-based dose regimen in high fat diet (HFD) mice and low fat diet (LFD) mice. We hypothesized that the FD-4 permeation result would be dose-dependent. Methods The two dose regimens were compared in HFD and LFD mice. Furthermore, we conducted a dose-response study to test the effect of a low or high dose of FD-4 in weight-stratified lean mice. Gene analysis of tight junctions was also carried out. Results The FD-4 intestinal permeability test was dose-dependent as we found a significant increase in plasma levels of FD-4 in obese mice with the bodyweight dose regimen. However, this difference was not detectable with the lean body mass dose regimen, even with variability-adjusted group sizes. However, the qPCR analysis revealed a decrease in tight junction gene expression in obese mice. Furthermore, we found a dose-dependent significant increase in FD-4 measured in plasma samples in lean mice. No significant difference in intestinal weight was observed between lean and obese mice. Conclusion Evaluation of the intestinal permeability by FD-4 with the typical bodyweight dose regimen in obese mice will be confounded by the significant difference in dose given when compared to a lean control group. If the test dose is based on lean body mass, no significant difference in intestinal permeability is observed, even with large group sizes. Furthermore, we showed a dose-dependent difference in plasma FD-4 levels in lean mice. Therefore, we conclude that the dose should be based on lean body mass for the FD-4 permeability test if mice with considerable obesity differences are to be compared or to use another test with fixed doses. |
| first_indexed | 2024-04-11T00:19:50Z |
| format | Article |
| id | doaj.art-8c16f181714e492db1c3c4c253eb04ca |
| institution | Directory Open Access Journal |
| issn | 2044-4052 |
| language | English |
| last_indexed | 2024-04-11T00:19:50Z |
| publishDate | 2023-01-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Nutrition & Diabetes |
| spelling | doaj.art-8c16f181714e492db1c3c4c253eb04ca2023-01-08T12:23:54ZengNature Publishing GroupNutrition & Diabetes2044-40522023-01-011311510.1038/s41387-022-00230-2The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese miceLouise M. Voetmann0Bidda Rolin1Rikke K. Kirk2Charles Pyke3Axel K. Hansen4Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of CopenhagenGlobal Drug Discovery, Novo Nordisk A/SGlobal Drug Discovery, Novo Nordisk A/SGlobal Drug Discovery, Novo Nordisk A/SDepartment of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of CopenhagenAbstract Aims To investigate the influence of the dose in the FITC-Dextran 4kDa (FD-4) permeability test in an obese mouse model, we tested the bodyweight dose regimen and a lean body mass-based dose regimen in high fat diet (HFD) mice and low fat diet (LFD) mice. We hypothesized that the FD-4 permeation result would be dose-dependent. Methods The two dose regimens were compared in HFD and LFD mice. Furthermore, we conducted a dose-response study to test the effect of a low or high dose of FD-4 in weight-stratified lean mice. Gene analysis of tight junctions was also carried out. Results The FD-4 intestinal permeability test was dose-dependent as we found a significant increase in plasma levels of FD-4 in obese mice with the bodyweight dose regimen. However, this difference was not detectable with the lean body mass dose regimen, even with variability-adjusted group sizes. However, the qPCR analysis revealed a decrease in tight junction gene expression in obese mice. Furthermore, we found a dose-dependent significant increase in FD-4 measured in plasma samples in lean mice. No significant difference in intestinal weight was observed between lean and obese mice. Conclusion Evaluation of the intestinal permeability by FD-4 with the typical bodyweight dose regimen in obese mice will be confounded by the significant difference in dose given when compared to a lean control group. If the test dose is based on lean body mass, no significant difference in intestinal permeability is observed, even with large group sizes. Furthermore, we showed a dose-dependent difference in plasma FD-4 levels in lean mice. Therefore, we conclude that the dose should be based on lean body mass for the FD-4 permeability test if mice with considerable obesity differences are to be compared or to use another test with fixed doses.https://doi.org/10.1038/s41387-022-00230-2 |
| spellingShingle | Louise M. Voetmann Bidda Rolin Rikke K. Kirk Charles Pyke Axel K. Hansen The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese mice Nutrition & Diabetes |
| title | The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese mice |
| title_full | The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese mice |
| title_fullStr | The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese mice |
| title_full_unstemmed | The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese mice |
| title_short | The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese mice |
| title_sort | intestinal permeability marker fitc dextran 4kda should be dosed according to lean body mass in obese mice |
| url | https://doi.org/10.1038/s41387-022-00230-2 |
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