Involvement of mTORC1 and 2 and PPARgamma in the regulation of leukocyte profile, recruitment and activation of brown adipose tissue and beige adipocytes induced by cold exposure

Abstract

The identification of good amounts of brown adipose tissue in humans along with beige adipocytes with the ability to express UCP-1 under demand, renewed the interest of studying nonshivering thermogenesis as a strategy to increase energy expenditure and counteract obesity. For this, it is important to develop strategies to recruit brown and beige adipocytes (increase cell number and thermogenic capacity), as well as, switch on and off thermogenesis under desired conditions. Therefore in the current proposal we will test the hypotheses that mTORC 1 and 2 and PPARgamma are important regulators of the leukocyte infiltration, metabolic changes, mitochondrial biogenesis in brown and white adipose tissue induced by cold exposure. For this, mice with gain and loss of function of mTORC1 and 2 and PPARgamma will be evaluated for leukocyte profile, recruitment (hyperplasia and hypertrophy, UCP-1 and mitochondrial content), thermogenic activity (heat production and oxygen consumption) and metabolism (glucose, fatty acids and amino acids) in brown and beige adipocytes after different periods of cold exposure. The involvement of specific leukocytes in the recruitment and activation of brown and beige adipocytes will be also investigated. (AU)