Effects of bone marrow with high myeloid ACE expression on the metabolism of adipose tissue and cardiovascular parameters in obese mice

• Grant number: 22/11063-2
• Support Opportunities: Scholarships abroad - Research
• Start date: May 01, 2023
• End date: April 30, 2024
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Erika Emy Nishi
• Grantee: Erika Emy Nishi
• Host Investigator: Kenneth Bernstein
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Institution abroad: Cedars-Sinai Medical Center, United States

Abstract

Several neurohumoral factors contribute to cardiovascular and adipose tissue dysfunction in obesity. In a previous study, we showed that retroperitoneal white adipose tissue innervation influences baroreflex control of blood pressure, circulating angiotensinogen, as well as inflammation markers in target organs in high-fat-fed (HF) rats with increased sympathetic drive. Moreover, it has been shown that macrophages regulate several metabolic processes including adipose tissue function. Previous work from Drs. Giani and Bernstein group showed that elevated angiotensin converting enzyme (ACE) expression in macrophages exerts profound phenotypic changes including an enhanced immune response against tumors and several pathogens, increased ATP production rates, augmented mitochondrial membrane potential, and increased oxidative metabolism compared to wild type macrophages. Considering the role of macrophages and renin-angiotensin system in metabolism regulation and cardiovascular system, the aim of this project is to evaluate whether increasing ACE expression in macrophages can affect adipose tissue, cardiovascular and renal function in HF mice. These studies will therefore provide insight into the role of bone marrow and myeloid ACE in controlling renal and cardiovascular parameters and lipid metabolism and recalibrating the whole-body metabolic profile during obesity. (AU)