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"Brite/beige adipocytes - a tool against obesity and diabetes - or not?"

Grant number: 19/19049-6
Support type:Scholarships abroad - Research
Effective date (Start): February 10, 2020
Effective date (End): August 09, 2020
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal Investigator:Rosemari Otton
Grantee:Rosemari Otton
Host: Barbara Cannon
Home Institution: Pró-Reitoria de Pós-Graduação e Pesquisa. Universidade Cruzeiro do Sul (UNICSUL). São Paulo , SP, Brazil
Local de pesquisa : Stockholm University, Sweden  

Abstract

Energy balance is defined by two components: energy intake and energy expenditure. Even minor but chronic perturbations in either of these two components can lead to an increase (obesity) or decrease in body weight. Obesity is not only a significant problem in itself but is also a major inducer of type 2 diabetes, cardiovascular disease and certain forms of cancer. At present, there is no satisfactory treatment for obesity and in reality little understanding of the cause of obesity, except for the self-evident statement that it arises from an imbalance between energy intake and energy expenditure. The identification of a novel type of adipocytes, i.e. the brite/beige adipocytes, that appear to possess the ability to increase energy expenditure and that are localized within the white adipose depots themselves, has provided a basis for studying new opportunities, both for counteracting the development of obesity and perhaps even for diminishing it in already obese persons. To confirm that issue the present project will utilize a mouse model manipulated physiologically and/or genetically to discriminate the importance of brite/beige cells and BAT to combat/counteract obesity and its comorbidities. We aim to evaluate the thermogenic competence of classical brown and brite/beige adipose depots in physiologically humanized mice to (re)gain high thermogenic capacity upon physiological or pharmacological treatments. For this purpose, we will use a UCP1-floxed mice with mice expressing Cre recombinase under the control of the Myf5 promoter (which is active in classical brown but not in brite/beige adipocytes) - BATUCP1-KO mice. It is the goal of this project to gain insight into the functional significance of the distinct populations of brite/beige and brown adipocytes but in a mouse model relevant for human physiology. Hopefully, through this project, we will gain knowledge regarding the magnitude of the beneficial metabolic effects exerted by the activity of each type of thermogenesis-competent adipocytes - classical brown and brite/beige. Considering the vast medical implications of the obesity epidemic and its co-morbidities, even modest amelioration of energy balance may be of significance. The studies of thermogenesis-competent adipocytes proposed here could represent one means of developing methods to accomplish such amelioration. The international interest in brite/beige adipose tissue is primarily driven by the anticipation that these tissues can be recruited to increase energy expenditure and thus restrict the development of obesity and even ameliorate existing obesity - with the medical purpose of diminishing obesity-driven comorbidities, notably, type 2 diabetes. This will be stringently evaluated. The present application does not involve any direct clinical studies but should point to future therapeutic possibilities.