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Dicer deletion in adipocytes and its influence in cardiovascular diseases

Grant number: 12/06238-6
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): June 01, 2012
Effective date (End): December 31, 2012
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Marcelo Alves da Silva Mori
Grantee:Adriano Silva Martins
Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:10/52557-0 - Identification of mechanisms responsible for beneficial effects of calorie restriction, AP.JP


Research Proposal - Postdoctoral Fellowship - FAPESP. Title: "Dicer Deletion in Adipocytes and Its Influence in Cardiovascular Diseases". Postdoctoral Candidate: Dr. Adriano Silva Martins. Supervisor: Dr. Marcelo Alves da Silva Mori. Institution: Biophysics Department - Federal University of Sao Paulo. Date:April, 2012. Abstract. Aging process and hypercaloric diet contribute to chronic diseases development, which can result in a cluster of metabolic and cardiovascular symptoms called "metabolic syndrome". Among these symptoms, stands the atherosclerosis, which is characterized by the formation of fat plaques with partial or total occlusion of the arteries lumen. Our data shows that the processing of miRNAs is diminished with the aging process in mice adipose tissue, and that this process can be reversed by caloric restriction. Adipose tissue has the potential to secrete molecules that may regulate the function of other tissues, participating actively in cardiovascular diseases genesis. Our previous data allow us to formulate the hypothesis that the reduction of miRNAs processing in adipose tissue can promote premature risk of age-related diseases, particularly cardiovascular diseases. With this in view, we will study animals (mice) unable to produce miRNAs in fat tissue-specific given the gene deletion that encodes Dicer, an enzyme critical towards mature miRNAs processing. Preliminary data show an elevation in serum levels of lipids and change to some hormones secretion that are involved in the metabolism of fats and carbohydrates in these animals, suggesting an environment favourable to the development of atherosclerosis. In this project we will challenge these mice with a Western diet rich in fats and/or infusion of Angiotensin II in pressor dose and/or a loss of function mutation in the gene apoE, and we will assess the development of atheroma plaques, plus serum metabolic profile in such animals. Our goal is to understand how the processing of miRNAs in adipose tissue controls the genesis of age-related diseases, identifying a new mechanism in the pathogenesis of atherosclerosis

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BRANDAO, BRUNA B.; MADSEN, SOREN; RABIEE, ATEFEH; OLIVERIO, MATTEO; RUIZ, GABRIEL P.; FERRUCCI, DANILO L.; BRANQUINHO, JESSICA L.; RAZOLLI, DANIELA; PINTO, SILAS; NIELSEN, THOMAS S.; et al. Dynamic changes in DICER levels in adipose tissue control metabolic adaptations to exercise. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 117, n. 38, p. 23932-23941, . (17/03423-0, 15/01316-7, 17/04377-2, 12/06238-6, 15/03292-8, 17/01184-9, 12/04079-8, 18/21635-8, 17/07975-8)

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