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. [Figure not available: see fulltext.].
Originalsprog | Engelsk |
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Artikelnummer | 1 |
Tidsskrift | Nutrition and Diabetes |
Vol/bind | 13 |
ISSN | 2044-4052 |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:We would like to thank colleagues at Novo Nordisk; M.B. Frederiksen, B.D. Frederiksen and R.B. Kildetoft for help with the in vivo studies, L.D. Agerholm and I.P Eliasen for help with gene expression assays and B. Brandrup, H.S. Nielsen, J.H. Rasmussen, S.J. Rasmussen and S.D. Høiberg for help with histology. Also, thanks to the operators in the Animal Unit, a special thanks to K.F. Bangshof and C.F.B. Clausen for assistance with PO dosing.
Publisher Copyright:
© 2023, The Author(s).