Analysis of de novo lipogenesis by nuclear magnetic ressonance (NMR) in mice with fatty liver chronically treated with fluoride for 20 days

• Grant number: 15/10988-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: September 12, 2015
• End date: October 15, 2015
• Field of knowledge: Biological Sciences - Biochemistry - Metabolism and Bioenergetics
• Principal Investigator: Marília Afonso Rabelo Buzalaf
• Grantee: Aline Dionizio Valle
• Supervisor: Rui Albuquerque Carvalho
• Host Institution: Faculdade de Odontologia de Bauru (FOB). Universidade de São Paulo (USP). Bauru , SP, Brazil
• Institution abroad: Universidade de Coimbra (UC), Portugal
• Associated to the scholarship: 13/25756-0 - Time effect of chronic fluoride treatment in mice with induced steatosis, BP.MS

Abstract

In an ongoing study it was noted that fluoride (F-) has a different action on the lipids profile depending on the exposure time as well as on the type of diet administered (normocaloric or hyperlipidic). The action of F- is more evident when it is administered for a period of 20 days. In this case, it was found an improvement in the lipids profile that was more evident when the animals were treated with a normocaloric diet (Presence). However, in animals treated with a hyperlipidic diet that had previously induced fatty liver, F did not provoke significant changes. However, it was observed that along time, F- accumulated in the body, indicating a possible binding between F- and lipids present in large quantities in the liver and in the bloodstream. Thus, the objective of this study is to evaluate the effect of chronic administration of F- in de novo lipogenesis in mice with hepatic steatosis induced by a hyperlipidic diet and compare these animals with those treated with normocaloric diet (Presence) for a period of 20 days. Twenty-four Swiss mice (26 g - 44 g) will be used. Initially, the animals (n = 24) will be divided into two groups (n = 12 per group) that will receive hyperlipidic diet for 30 days, to induce hepatic steatosis, and deionized water (Group I) or normocaloric diet and deionized water (Group II). After this period, the group I will be divided into two groups (n = 6 per group) according to the type of water administered, as follows: deionized water (group A) and water containing 50 ppm F- (Group B). Group II will also be divided into two groups (n = 6 per group) according to the type of water administered, as follows: deionized water (Group C) and water containing 50 ppm F- (Group D). In both cases, during the 20 days of treatment, the same diet previously administered will be maintained. Three days before euthanasia, the animals will receive by "gavage" a volume of 2H2O (deuterium oxide) so as to obtain an enrichment of body water deuterium around 3% (assuming 75% of body water). For the remainder of the study, 3% 2H2O will be added in the drinking water to keep the body water enrichment throughout the study. After the experimental period, the animals will be anesthetized with 10mg/kg body weight Anasedan + 100mg/kg of ketamine hydrochloride (Vetaset) to collect the liver and blood. Fluoride will be analyzed in plasma and liver. In the remaining liver tissue, lipids will be extracted for the analysis of lipids enriched in deuterium by nuclear magnetic ressonance. The evaluation of this enrichment makes it possible to identify and quantify the pathways of de novo lipogenesis. After verification of normality and homoscedasticity of the data, they will be submitted to appropriate statistical analysis (p <0.05). (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

DIONIZIO, ALINE; BARBOSA SILVA PEREIRA, HELOISA APARECIDA; ARAUJO, TAMARA TEODORO; SABINO-ARIAS, ISABELA TOMAZINI; FERNANDES, MILENI SILVA; OLIVEIRA, KARINA APARECIDA; RAYMUNDO, FABIELLE SALES; CESTARI, TANIA MARY; NOGUEIRA, FERNANDO NEVES; CARVALHO, RUI ALBUQUERQUE; et al. Effect of Duration of Exposure to Fluoride and Type of Diet on Lipid Parameters and De Novo Lipogenesis. BIOLOGICAL TRACE ELEMENT RESEARCH, v. 190, n. 1, p. 157-171, JUL 2019. (15/10988-9, 13/25756-0)