Advanced search
Start date
Betweenand

Evaluation of serum factors effects obtained from mice with and without predisposition to obesity on inflammatory aspects in microglia line and hypothalamic neurons

Grant number: 17/08200-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2017
Effective date (End): November 30, 2018
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Licio Augusto Velloso
Grantee:Davi Sidarta Vitória Rodrigues de Oliveira
Home Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:13/07607-8 - OCRC - Obesity and Comorbidities Research Center, AP.CEPID

Abstract

Obesity is a condition which involves several body systems and is associated with a large group of comorbidities. It is defined by the World Health Organization as an anormal or excessive body fat accumulation that represents risks considering one's health, and characterized by a body-mass-index greater than 30,0. Epidemiological studies point that, according to previsions, by 2030, 38.1% of world population will be presented with overweight, and 19.7% of world population will suffer from obesity. Big data studies pointed that obesity strongly increases relative risks for major diseases development - such as hypertension, coronary artery disease, pulmonary embolism, stroke, cancer (breast, colorectal, esophagus, kidney, ovary, pancreas and prostate), asthma, gallbladder, which costs heavily to national health systems and impacts greatly on people's well-being. Body weight is regulated by complex and intricate interactions between environmental, genetics and behavioral factors. The center of this finely adjusted mechanism is the hypothalamus, a little diencephalic area. Although behavioral aspects such as unbalanced, excessive feeding, and a lack of physical activities which characterizes sedentarism, have long been pointed as the major causes of obesity, recent studies have shed new light upon this matter. It has been demonstrated that the disruption of energy homeostasis is a more complex and intricate process, which involves leptin and insulin (adiposity signals) resistance and hormonal disbalance involving saciety signals such as colecistoquinin (CCK), glucagon-like-peptide-1 (GLP-1) and ghrelin. Among this several factors, leptin resistance - and, secondly, insulin resistance - have been shown to be protagonists of the obesogenic process. This signals, during normal energy homeostasis, act on the hypothalamus so as to signal to the Central Nervous System the current body energetic status. Obese individuals have been shown to be resistant to these hormones, a process that involves a subclinic, chronic inflammatory process, first at the hypothalamus, and later, at other organs, such as liver and white adipose tissue. This occurs due to a cross-talk between inflammatory signaling and leptin and insulin signaling pathways, notedly because of the activation of Toll-like receptors. In this context, the inflammatory response pattern and the hypothalamus reaction to these stimulus are fundamental. Face to these facts, abundant research is being conducted on this subject, on the hope that better knowledge of this matter may lead to a better comprehension of obesity, its physiopathology, its associated comorbidities and potential therapeutic targets for best clinical care. This project intends to study this subject more deeply. For that, we will use seric factors from the blood obtained from mouses either prone or resistant to obesity development to treat hypothalamic cells and evaluate its response. For that, we shall use polymerase chain reaction to evaluate how the treatment modulates certain genes expression, notedly the ones involved in inflammatory signaling and pathways. (AU)