Dexamethasone-Induced Adipose Tissue Redistribution and Metabolic Changes: Is Gene Expression the Main Factor? An Animal Model of Chronic Hypercortisolism

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Silva, Flaviane de Fatima ; Medeiros Komino, Ayumi Cristina ; Andreotti, Sandra ; Reis, Gabriela Boltes ; Caminhotto, Rennan Oliveira ; Landgraf, Richardt Gama ; de Souza, Gabriel Orefice ; Laurato Sertie, Rogerio Antonio ; Collins, Sheila ; Donato, Jose, Jr. ; Lima, Fabio Bessa

• Document type: Journal article
• Source: BIOMEDICINES; v. 10, n. 9, p. 23-pg., 2022-09-01.

Abstract

Chronic hypercortisolism has been associated with the development of several metabolic alterations, mostly caused by the effects of chronic glucocorticoid (GC) exposure over gene expression. The metabolic changes can be partially explained by the GC actions on different adipose tissues (ATs), leading to central obesity. In this regard, we aimed to characterize an experimental model of iatrogenic hypercortisolism in rats with significant AT redistribution. Male Wistar rats were distributed into control (CT) and GC-treated, which received dexamethasone sodium phosphate (0.5 mg/kg/day) by an osmotic minipump, for 4 weeks. GC-treated rats reproduced several characteristics observed in human hypercortisolism/Cushing's syndrome, such as HPA axis inhibition, glucose intolerance, insulin resistance, dyslipidemia, hepatic lipid accumulation, and AT redistribution. There was an increase in the mesenteric (meWAT), perirenal (prWAT), and interscapular brown (BAT) ATs mass, but a reduction of the retroperitoneal (rpWAT) mass compared to CT rats. Overexpressed lipolytic and lipogenic gene profiles were observed in white adipose tissue (WAT) of GC rats as BAT dysfunction and whitening. The AT remodeling in response to GC excess showed more importance than the increase of AT mass per se, and it cannot be explained just by GC regulation of gene transcription. (AU)

• FAPESP's process: 18/16856-5 - Study of alterations in lipolytic response and glyceroneogenesis in adipose territories of different anatomical locations induced by chronic iatrogenic hypercortisolism
• Grantee: Ayumi Cristina Medeiros Komino
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• FAPESP's process: 16/25129-4 - Iatrogenic Chronic Hypercortisolism and its implications to the adipose tissue plasticity an analysis of the dynamics of adipose tissue distribution in an experimental model of Cushing's Syndrome
• Grantee: Fabio Bessa Lima
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 18/11145-3 - Study of alterations in thermogenic capacity and regulation of browning / whitening in adipose territories of different anatomical locations induced by chronic iatrogenic hypercortisolism
• Grantee: Flaviane de Fatima Silva
• Support Opportunities: Scholarships in Brazil - Doctorate