Study of the role of GCN1 in the genesis of metabolic diseases in mice

• Grant number: 15/03292-8
• Support type: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2015
• Effective date (End): February 28, 2019
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marcelo Alves da Silva Mori
• Grantee: Beatriz Alves Guerra
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Metabolic diseases are an important public health issue. Obesity and type 2 diabetes are the most common among these diseases. It is thus necessary to identify new targets to treat and/or prevent metabolic diseases. The adipose tissue and skeletal muscle are important to maintain metabolic homeostasis, as they are fundamental in nutrient partitioning and essential in energy balance control. The GCN1-GCN2-eIF2 alfa (General Control Nonderepressible 1, General Control Nonderepressible 2 and Eukaryotic Translation Initiation Factor 2 alfa) pathway is ubiquitously expressed and act in the yeast in response to amino acid deprivation to activate an adaptive metabolic response that includes the inhibition of protein synthesis and the expression of the transcription factor ATF4. This study aims to investigate the importance of this pathway, particularly GCN1 in adipocytes and muscle cells, to the genesis of metabolic diseases. We will knockout GCN1 in adipose tissue (both in mature adipocytes and adipocyte precursors) or muscle (myocyte precursor) of mice, conditionally or constitutively, and will study the metabolic phenotypes of these animals in response to different nutritional interventions. We intend to characterize a new mechanism of metabolic regulation and a new target for drugs to treat obesity and type 2 diabetes. (AU)

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)

GUERRA, BEATRIZ A.; BRANDAO, BRUNA B.; PINTO, SILAS S.; SALGUEIRO, WILLIAN G.; DE-SOUZA, EVANDRO A.; REIS, FELIPE C. G.; BATISTA, THIAGO M.; CAVALCANTE-SILVA, VANESSA; D'ALMEIDA, VANIA; CASTILHO, BEATRIZ A.; CARNEIRO, EVERARDO M.; ANTEBI, ADAM; FESTUCCIA, WILLIAM T.; MORI, MARCELO A. Dietary sulfur amino acid restriction upregulates DICER to confer beneficial effects. MOLECULAR METABOLISM, v. 29, p. 124-135, NOV 2019. Web of Science Citations: 0.

BRANDAO, BRUNA B.; GUERRA, BEATRIZ A.; MORI, MARCELO A. Shortcuts to a functional adipose tissue: The role of small non-coding RNAs. REDOX BIOLOGY, v. 12, p. 82-102, AUG 2017. Web of Science Citations: 24.