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The impact of cholesteryl ester transfer protein (CETP) expression on adiposity in thermoneutral condition and obesogenic diet: focus on white adipose tissue

Grant number: 19/02340-0
Support type:Scholarships in Brazil - Master
Effective date (Start): July 01, 2019
Effective date (End): February 28, 2021
Field of knowledge:Biological Sciences - Physiology - General Physiology
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Helena Coutinho Franco de Oliveira
Grantee:Júlia Zago Castelli
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated research grant:17/17728-8 - Mitochondrial function and dysfunction: implications for aging and associated diseases, AP.TEM

Abstract

The excess of fat accumulation causes cardio-metabolic disorders, which harm individual health. Previous data from our lab have shown that cholesteryl ester transfer protein (CETP) expression may play a relevant role in reducing adiposity. CETP promotes the exchange of triglycerides by cholesterol between HDL and lipoproteins containing apoB in plasma. This action may enhance the atherosclerosis risk, because of the reduction of HDL-cholesterol plasma levels. However, we have demonstrated that mice overexpressing CETP fed with regular low fat diet have less adipose tissue mass (~30%) and leptin plasma levels (40%) than non-transgenic control mice (NTg). Our data also show that the motor and food behavior (spontaneous activity, food intake and fat excretion), lipogenesis, exogenous lipid absorption and glucose uptake were not affected by CETP. We have verified that CETP reduces adiposity by increasing lipolysis and body energy expenditure, demonstrated by functional assays (plasma glycerol release and oxygen consumption) and molecular assays (increase in the expression of genes and proteins: HSL, ATGL, B3AR, UCP1). Brown adipose tissue (BAT) thermogenesis could account, at least in part, by the increase in metabolic rate, which was verified by higher interescapular BAT temperature and oxygen consumption. In this project, we will evaluate the role of CETP in obesogenic conditions, i.e., under high fat and high cholesterol diet (60% of calories as fat and 1% cholesterol) and in thermo-neutrality (30ºC).