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RANKL and osteoprotegerin expression profile in hypercaloric diet

Grant number: 16/06532-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2016
Effective date (End): April 30, 2017
Field of knowledge:Biological Sciences - Biochemistry - Metabolism and Bioenergetics
Principal Investigator:Mariana Kiomy Osako
Grantee:Karen Cristine de Oliveira Santos Ferreira
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:14/11092-6 - RANKL system in phenotypic switch of macrophages in adipose tissue inflammation, AP.JP

Abstract

The soluble and secreted protein Osteoprotegerin (OPG) is a decoy receptor for RANKL (receptor activator of NFkB ligand) that inhibits its binding to the membrane bound receptor RANK (receptor activator of NFkB). High serum osteoprotegerin (OPG) level has been associated with type 2 diabetes mellitus (T2DM), but the biological explanation for the rise of OPG level remains unclear: Is OPG beneficial or deleterious for T2DM? How the therapies should approach the RANK-RANKL-OPG axis? T2DM is a multifactorial disease, and the development of insulin resistance in adipose tissue has been described as the trigger event, since adipose tissue, liver and skeletal muscle are the three major targets for insulin in the glucose metabolism. High fat diet induced-hypertrophied adipocytes eventually undergo lipolysis and release large quantities of free fatty acids that recruit macrophages and lymphocytes. The local pro-inflammatory cytokines such as TNF-a impair the insulin signaling in adipocytes and worse the insulin resistance in adipose tissue. In a recent article, we demonstrated the anti-inflammatory action of RANKL in a murine model of brain ischemia. And preliminary data have shown that OPG-/- mice are resistant to the development of high fat diet induced-T2DM. The objective of the present project of Scientific Initiation is to quantify the serum levels of OPG and RANKL during the 3 months of high fat diet, and evaluate their gene expression on the visceral adipose tissue. And, eventually, elucidate the contribution of OPG derived from adipose tissue in animals with insulin resistance and T2DM. (AU)