Adaptive responses of the ileum of NOD mice to low‐dose fluoride: A proteomic exploratory study

Fluoride (F) has been employed worldwide to control dental caries. More recently, it has been suggested that the consumption of low doses of F in the drinking water may reduce blood glucose levels, introducing a new perspective for the use of F for the management of blood glucose. However, the exact...

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Published in:	Cell biochemistry and function Vol. 42; no. 2; pp. e3976 - n/a
Main Authors:	Trevizol, Juliana S., Buzalaf, Nathalia R., Dionizio, Aline, Delgado, Aislan Q., Lara, João P. Z., Magalhães, Ana C., Bosqueiro, José R., Buzalaf, Marília A. R.
Format:	Journal Article
Language:	English
Published:	England Wiley Subscription Services, Inc 01-03-2024
Subjects:	Actin Antioxidants Blood Blood glucose Blood levels Consumption Dental caries diabetes Diabetes mellitus Drinking water Energy metabolism Enzymes epigenetic Females Fluoridation fluoride Fluoride treatments Fluorides Glucose glucose homeostasis Histones Homeostasis Ileum Intestine Isoforms Metabolism Protein biosynthesis Protein synthesis Proteins Proteomics Safety Small intestine Water supply ileum glucose homeostasis fluoride epigenetic diabetes
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Summary:	Fluoride (F) has been employed worldwide to control dental caries. More recently, it has been suggested that the consumption of low doses of F in the drinking water may reduce blood glucose levels, introducing a new perspective for the use of F for the management of blood glucose. However, the exact mechanism by which F affects blood glucose levels remains largely unexplored. Given that the small gut plays a pivotal role in glucose homeostasis, the aim of this study was to investigate the proteomic changes induced by low doses of F in the ileum of female nonobese‐diabetic (NOD) mice. Forty‐two female NOD mice were divided into two groups based on the F concentration in their drinking water for 14 weeks: 0 (control) or 10 mgF/L. At the end of the experimental period, the ileum was collected for proteomic and Western blot analyses. Proteomic analysis indicated an increase in isoforms of actin, gastrotropin, several H2B histones, and enzymes involved in antioxidant processes, as well as a decrease in enzymes essential for energy metabolism. In summary, our data indicates an adaptive response of organism to preserve protein synthesis in the ileum, despite significant alterations in energy metabolism typically induced by F, therefore highlighting the safety of controlled fluoridation in water supplies. Significance statement The consumption of low doses of fluoride in the drinking water may increase insulin sensitivity or reduce blood glucose levels. However, the exact mechanisms by which fluoride influences glucose homeostasis remain unclear. Considering that the small intestine is central to glucose homeostasis, here we investigated the proteomic changes induced by low doses of fluoride (similar to those added to the drinking water) in the ileum of NOD mice. We found an increase in gastrotropin, histones, and antioxidant enzymes, and a decrease in enzymes involved in energy metabolism. These results indicate an adaptive response of the organism to preserve protein synthesis in the ileum, despite significant alterations in energy metabolism, therefore highlighting the safety of controlled fluoridation of water supplies. Further studies employing specialized techniques should be developed to unravel specific pathways of the mechanisms by which fluoride affects glucose homeostasis.
Bibliography:	Juliana S. Trevizol and Nathalia R. Buzalaf contributed equally to this work. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0263-6484 1099-0844
DOI:	10.1002/cbf.3976