Effects of fast mimicking diet on REVERB signaling pathway and regulation of lipid metabolism in the liver of diet-induced obese C57BL/J6 mice

• Grant number: 23/06146-9
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: September 01, 2023
• End date: February 29, 2024
• Field of knowledge: Health Sciences - Nutrition
• Principal Investigator: José Rodrigo Pauli
• Grantee: Gabriel Calheiros Antunes
• Supervisor: Valter Longo
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Institution abroad: University of Southern California (USC), United States
• Associated to the scholarship: 21/13847-8 - Effects of time-restricted feeding combined with physical exercise or REV-ERB agonist on obesity and liver metabolism of male and female mice, BP.MS

Abstract

Obesity is a serious public health problem characterized by excessive accumulation of body fat, involving a wide variety of factors (genetic, metabolic, social, behavioral, psychological, and environmental), with worldwide scope and rates that have almost doubled in the last 30 years (1,2). The meta-inflammation present in obesity induces impairments in insulin signaling and action, with notable disturbances in metabolic processes in the liver (3-5). Time-restricted feeding (TRF) has been a strategy adopted to minimize the impacts of obesity (6,7). In recent decades, a large number of studies have been trying to investigate the physiological and molecular effects of this type of intervention in experimental models in order to verify the potential benefits on the organism and in the prevention and treatment of metabolic disorders linked to diseases such as obesity and type 2 diabetes (6-9). Similarly, the Fast Mimicking Diet (FMD) is an effective nutritional strategy used to increase health span and treat diseases associated with aging. Presenting the same effects as TRF, FMD is a strategy that has greater adherence due to not requiring dietary restriction (10). Additionally, another strategy with potential for weight loss and improved metabolism involves actions capable of promoting the regulation of genes and proteins related to the circadian cycle. Specifically, the REVERB signaling pathway has been shown to be an interesting target in both mechanisms and has an impact on weight gain and metabolic health (11,12). The REV-ERB protein, encoded by the Nr1d1 gene, is related to the regulation of clock genes at the level of the central nervous system, as well as having a direct relationship in controlling other genes located in peripheral tissues, including the liver (13,14). In that way, the research project aims to investigate the effects of FMD in the REVERB signaling pathway as well others clock related, lipogenic and fatty acid oxidation pathways in the liver of mice. Therefore, experiments will be carried out in C57BL/J6 mice submitted to an FMD protocol. The effects of FMD treatment will be evaluated through lipogenic and fatty acid oxidation signaling pathways as well REVERB pathway and related clock genes. The animals will be euthanized 4h of fasting, and the liver tissue will be extracted for RT-qPCR and Western Blot analysis. It is expected that the results obtained from this study may help to elucidate how FMD can impact the REVERB pathway and regulate lipid metabolism. (AU)