Effects of Sleep restriction on development of insulin resistance in peripheral tissues, mediated by Entotoxin in mices

• Grant number: 16/19013-3
• Support Opportunities: Regular Research Grants
• Duration: February 01, 2017 - January 31, 2019
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Daniel Paulino Venancio
• Grantee: Daniel Paulino Venancio
• Host Institution: Faculdade de Medicina do ABC (FMABC). Organização Social de Saúde. Fundação do ABC. Santo André , SP, Brazil

Abstract

In the modern society, the economic necessities, use of technology and shift work schedule induced a change in the sleep behavior, by reducing the hours spent in sleep. Epidemiological studies have associated sleeplessness to the high risk of cardiovascular and metabolic diseases. Studies has demonstrated that the consumption of high fat diet associated to a fragmentation or deprivation of sleep increased the adipose tissue as well as inflammatory processes. Authors are associating the chronic and silent inflammatory condition to a reduced insulin receptor signaling in skeletal muscle, fat tissue and liver. Furthermore, this inflammatory condition may interfere with the functionality of pancreatic beta cells, by reducing the release of insulin and contributing to the development of type II diabetes. Recent studies show that sleep deprivation in rats and mice induces increased production of pro-inflammatory cytokines by adipose tissue as well as an augmented endotoxin plasma levels. It is well known that endotoxin binds to the Toll-like receptor 4 (TLR-4), thus activating the NF-kB signaling pathway and leading to the production of pro-inflammatory cytokines. So, this project aims to study the mechanism by which sleep deprivation associated to a high fat diet lead to systemic inflammation and insulin resistance. To address these questions, wild-type and TLR-4 knockout mice will be feed with a high fat diet during a sleep restriction protocol for 21 days. The glycemia and the plasmatic levels of endotoxin and pro-inflammatory cytokine will be measured in the end of sleep restriction protocol. The NF-kB and insulin receptor signaling pathways will be analyzed in the fat tissue, skeletal muscle and liver. (AU)