Connections between apoptosis pathways, endoplasmic reticulum stress and autophagy in adipose tissue of obese animals

• Grant number: 11/17927-4
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2012
• End date: March 31, 2014
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eliana Pereira de Araujo
• Grantee: Eliana Pereira de Araujo
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Obesity and diabetes are among the most prevalent diseases in the world. The mechanisms responsible for the frequent clinical association between these two conditions are not completely known. According to animal models studies, leptin and insulin resistance in hypothalamic areas causes an imbalance in energy homeostasis favoring the gradual weight gain. Hypertrophied adipose tissue macrophages recruited to generate a systemic subclinical inflammation. The activation of inflammatory pathways in muscle cells, liver and fat, results in deterioration of insulin signal, and eventually in hyperglycemia. Recent studies reveal that in adipocytes, activation of inflammatory pathways results from a complex association between signals transduced by extracellular TLR4 receptors and induction of endoplasmic reticulum stress. With progression of the inflammatory signal, pro-apoptotic pathways activated, however, the links between inflammatory signaling, reticulum stress and apoptosis in the context of obesity are not completely known. This project aims to determine the role of autophagy in the connection between the events described above. Autophagy is a complex cellular process that provides energy for the cell from the degradation of organelles. In this work obese and diet-induced autophagy, endoplasmic reticulum stress and apoptosis will be studied by real-time PCR, western blot and electron microscopy in animal models of obesity. We believe that the characterization of autophagy and endoplasmic reticulum stress provide advance knowledge of the mechanisms involved in the connection between obesity, inflammation and insulin resistance. (AU)