Study of alterations in thermogenic capacity and regulation of browning / whitening in adipose territories of different anatomical locations induced by chronic iatrogenic hypercortisolism

Abstract

Cushing's syndrome is an endocrine disorder caused by chronic exposure to glucocorticoids. Its etiology is varied, but the most common cause is prolonged use of synthetic glucocorticoids - the iatrogenic hypercortisolism. One of the most important characteristics of this syndrome is the rupture of the circadian rhythm of glucocorticoid release and hormonal action, seriously disturbing the hypothalamic-pituitary-adrenal axis and triggering several systemic alterations such as glucose intolerance, insulin resistance, dyslipidemia and central fat distribution. The increase in central adiposity in hypercortisolism is not yet fully understood, but is possibly related to alterations in the balance of lipolysis / lipogenesis and adipogenesis / apoptosis in different adipose depots, as well as alterations in the differentiation of beige adipocytes - the browning, or reduction of thermogenic function of beige and brown adipocytes - the whitening. Evidence suggests that weight gain by increasing white adipose tissue caused by glucocorticoids has a suppressive effect on browning and promotes whitening, mainly by reducing UCP1 expression. At the same time, the inhibition of browning and, consequently, its thermogenic effects on white adipose tissue seems to be related to increased central adiposity. In summary, it is still unclear if browning inhibition and/or whitening enhancement is a cause or consequence of central fat accumulation in iatrogenic hypercortisolism. Therefore, the objective of the present project will be to investigate how the browning and whitening processes are related to the adipose redistribution in an experimental model of iatrogenic hypercortisolism established in our laboratory.