Effects of time-restricted feeding on insulin sensitivity and secretion in mice fed with a high-fat diet

• Grant number: 24/19108-0
• Support Opportunities: Scholarships abroad - Research Internship - Master's degree
• Start date: April 01, 2025
• End date: September 30, 2025
• Field of knowledge: Health Sciences - Nutrition
• Principal Investigator: José Rodrigo Pauli
• Grantee: Guilherme Correia Ferri Antonio
• Supervisor: Amandine Chaix
• Host Institution: Faculdade de Ciências Aplicadas (FCA). Universidade Estadual de Campinas (UNICAMP). Limeira , SP, Brazil
• Institution abroad: University of Utah (U), United States
• Associated to the scholarship: 23/03677-3 - Effects of time-restricted feeding combined with physical exercise in the treatment of obesity and non-alcoholic fatty liver disease of obese mice, BP.MS

Abstract

Obesity is a chronic multifactorial disease characterized by excessive body fat accumulation, and its increasing prevalence has become a serious public health issue. In addition to being associated with metabolic disorders such as dyslipidemia, arterial hypertension, and glucose intolerance, obesity is a risk factor for insulin resistance and type 2 diabetes. Insulin resistance, triggered by inflammation in peripheral tissues, leads to a compensatory increase in insulin secretion by beta cells in the pancreatic islets. The resulting chronic hyperglycemia, combined with lipotoxicity due to the accumulation of free fatty acids (FFA), is related to the loss of beta cell function, contributing to the development of type 2 diabetes.Dietary strategies, such as time-restricted feeding (TRF), have attracted increasing attention from the scientific community due to their potential benefits in treating and preventing obesity. TRF involves limiting the eating window to between 8 and 12 hours without the need to control the amount of food consumed. Studies have shown that this approach can reduce body weight, fasting blood glucose levels, and improve lipid and inflammatory profiles in experimental models. Additionally, there is evidence that TRF reduces fat accumulation in the liver, positively impacting diabetes prevention.Despite these advances, knowledge about the effects of TRF on the endocrine function of the pancreas, especially regarding the insulin secretion capacity of beta cells, remains limited. Our hypothesis is that dietary interventions like TRF can improve insulin sensitivity, preserve islet function, and thus regulate insulin secretion and glycemic homeostasis.In this project, we will analyze insulin secretion by pancreatic islets and peripheral insulin sensitivity in obese diabetic mouse models (DIO) subjected to a TRF protocol. To evaluate glucose intolerance associated with defects in islet insulin secretion, we will use advanced techniques, including an in vivo glucose-stimulated insulin secretion (GSIS) assay.