TY - JOUR
T1 - Glucocorticoid modulates oxidative and thermogenic function of rat brown adipose tissue and human brown adipocytes
AU - Bolin, Anaysa Paola
AU - de Fatima Silva, Flaviane
AU - Salgueiro, Rafael Barrera
AU - dos Santos, Bruna Araújo
AU - Komino, Ayumi Cristina Medeiros
AU - Andreotti, Sandra
AU - de Sousa, Érica
AU - de Castro, Érique
AU - Real, Caroline Cristiano
AU - de Paula Faria, Daniele
AU - Souza, Gerson Profeta
AU - Camara, Henrique
AU - Sorgi, Carlos Arterio
AU - Tseng, Yu Hua
AU - Lima, Fábio Bessa
AU - Rodrigues, Alice Cristina
N1 - Publisher Copyright:
© 2024 Wiley Periodicals LLC.
PY - 2024/9
Y1 - 2024/9
N2 - Chronic and excessive glucocorticoid (GC) exposure can cause Cushing's syndrome, resulting in fat accumulation in selected body areas. Particularly in the brown adipose tissue (BAT), GC acts negatively, resulting in whitening of the tissue. We hypothesized that dysregulation of microRNAs by GC could be an additional mechanism to explain its negative actions in BAT. Male Wistar rats were divided into two groups: (1) Control sham and (2) GC group that was administered dexamethasone 6.25 mg/200 μL via osmotic pump implantation over 28 days. After this period, the animals were euthanized and BAT tissue was properly stored. Human fat cells treated with dexamethasone were used to translate the experimental results found in animals to human biology. GC-treated rat BAT presented with large lipid droplets, severely impaired thermogenic activation, and reduced glucose uptake measured by 18F-FDG PET/CT. GC exposure induced a reduction in the mitochondrial OXPHOS system and oxygen consumption. MicroRNA profiling of BAT revealed five top-regulated microRNAs and among them miR-21-5p was the most significantly upregulated in GC-treated rats compared to the control group. Although upregulation of miR-21-5p in the tissue, differentiated primary brown adipocytes from GC-treated rats had decreased miR-21-5p levels compared to the control group. To translate these results to the clinic, human brown adipocytes were treated with dexamethasone and miR-21-5p inhibitor. In human brown cells, inhibition of miR-21-5p increased brown adipocyte differentiation and prevented GC-induced glucose uptake, resulting in a lower glycolysis rate. In conclusion, high-dose GC therapy significantly impacts brown adipose tissue function, with a notable association between glucose uptake and miR-21-5p.
AB - Chronic and excessive glucocorticoid (GC) exposure can cause Cushing's syndrome, resulting in fat accumulation in selected body areas. Particularly in the brown adipose tissue (BAT), GC acts negatively, resulting in whitening of the tissue. We hypothesized that dysregulation of microRNAs by GC could be an additional mechanism to explain its negative actions in BAT. Male Wistar rats were divided into two groups: (1) Control sham and (2) GC group that was administered dexamethasone 6.25 mg/200 μL via osmotic pump implantation over 28 days. After this period, the animals were euthanized and BAT tissue was properly stored. Human fat cells treated with dexamethasone were used to translate the experimental results found in animals to human biology. GC-treated rat BAT presented with large lipid droplets, severely impaired thermogenic activation, and reduced glucose uptake measured by 18F-FDG PET/CT. GC exposure induced a reduction in the mitochondrial OXPHOS system and oxygen consumption. MicroRNA profiling of BAT revealed five top-regulated microRNAs and among them miR-21-5p was the most significantly upregulated in GC-treated rats compared to the control group. Although upregulation of miR-21-5p in the tissue, differentiated primary brown adipocytes from GC-treated rats had decreased miR-21-5p levels compared to the control group. To translate these results to the clinic, human brown adipocytes were treated with dexamethasone and miR-21-5p inhibitor. In human brown cells, inhibition of miR-21-5p increased brown adipocyte differentiation and prevented GC-induced glucose uptake, resulting in a lower glycolysis rate. In conclusion, high-dose GC therapy significantly impacts brown adipose tissue function, with a notable association between glucose uptake and miR-21-5p.
KW - adipose tissue
KW - Cushing's syndrome
KW - dexamethasone
KW - miR
KW - miR-21-5p
UR - https://www.scopus.com/pages/publications/85200261615
U2 - 10.1002/jcp.31397
DO - 10.1002/jcp.31397
M3 - Journal article
C2 - 39091018
AN - SCOPUS:85200261615
SN - 0021-9541
VL - 239
SP - 1
EP - 12
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 9
ER -