Acute exposure to Fluorotelomer alcohol (FTOH) and fluoride via Free Fatty Acid Receptor 1 (GPR40) in Beta cells

• Grant number: 24/07452-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2024
• End date: August 31, 2025
• Field of knowledge: Health Sciences - Dentistry - Social and Preventive Dentistry
• Principal Investigator: Marília Afonso Rabelo Buzalaf
• Grantee: Juliana Sanches Trevizol
• Supervisor: Maiko Suzuki
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Institution abroad: Nova Southeastern University, United States
• Associated to the scholarship: 20/04369-2 - Effect of fluoride on parameters related to glucose homeostasis: unraveling mechanisms, BP.DR

Abstract

Fluoride (F) is an important agent for dental caries control, being applied preventively in artificially fluoridated public water supplies. Animal studies from our group have shown that low doses of fluoride in drinking water, similar to those found in public water supplies, increase insulin sensitivity and reduce blood glucose levels in diabetic rodents. Recently, we observed that NOD mice exposed to low doses of fluoride exhibit a decrease in the expression of phosphoenolpyruvate carboxykinase (PEPCK) in the liver. Per-and-polyfluoroalkyl substances (PFAS) are used in various commercial and industrial applications with potential risks to environmental health and are apparently widespread in oceans, streams, and groundwater. Drinking water is a common exposure route, and increased monitoring has revealed elevated concentrations worldwide. Fluorotelomer alcohols (FTOHs) are direct precursors of PFOA and PFOS and can induce ameloblast degeneration, hepatotoxicity, and increased cancer cell proliferation. This led us to investigate the in vitro effects of acute exposure to 8:2 FTOH and NaF on insulin secretion, suggesting the GRP40 pathway as a mediator, aiming to provide an innovative study that has not yet been reported in the literature. The results to be obtained are of great relevance to public health, as fluoridation of public water supplies, in addition to controlling dental caries, may also play an important role in glucose homeostasis, besides being able to investigate the effects of exposure to 8:2 FTOH on pancreatic cells.