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

• Tipo de documento: Artigo Científico
• Fonte: BIOMEDICINES; v. 10, n. 9, p. 23-pg., 2022-09-01.

Resumo

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)

• Processo FAPESP: 18/16856-5 - Estudo das alterações na resposta lipolítica e na gliceroneogênese em territórios adiposos de diferentes localizações anatômicas induzidas pelo hipercortisolismo iatrogênico crônico
• Beneficiário: Ayumi Cristina Medeiros Komino
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 16/25129-4 - Hipercortisolismo Crônico Iatrogênico e suas implicações para a plasticidade do tecido adiposo uma análise da dinâmica da distribuição adiposa em um modelo experimental de Síndrome de Cushing
• Beneficiário: Fabio Bessa Lima
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 18/11145-3 - Estudo das alterações na capacidade termogênica e na regulação do browning/whitening em territórios adiposos de diferentes localizações anatômicas induzidas pelo hipercortisolismo iatrogênico crônico
• Beneficiário: Flaviane de Fatima Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado