Kinin B1 receptor deficiency promotes enhanced adipose tissue thermogenic response to ß3-adrenergic stimulation.
Inflamm Res
; 73(9): 1565-1579, 2024 Sep.
Article
in En
| MEDLINE
| ID: mdl-39017739
ABSTRACT
OBJECTIVE AND DESIGN:
Kinin B1 receptor (B1R) has a key role in adipocytes to protect against obesity and glycemic metabolism, thus becoming a potential target for regulation of energy metabolism and adipose tissue thermogenesis. MATERIAL ORSUBJECTS:
Kinin B1 knockout mice (B1KO) were subjected to acute induction with CL 316,243 and chronic cold exposure.METHODS:
Metabolic and histological analyses, gene and protein expression and RNA-seq were performed on interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) of mice.RESULTS:
B1KO mice, under acute effect of CL 316,243, exhibited increased energy expenditure and upregulated thermogenic genes in iWAT. They were also protected from chronic cold, showing enhanced non-shivering thermogenesis with increased iBAT mass (~ 90%) and recruitment of beige adipocytes in iWAT (~ 50%). Positive modulation of thermogenic and electron transport chain genes, reaching a 14.5-fold increase for Ucp1 in iWAT. RNA-seq revealed activation of the insulin signaling pathways for iBAT and oxidative phosphorylation, tricarboxylic acid cycle, and browning pathways for iWAT.CONCLUSION:
B1R deficiency induced metabolic and gene expression alterations in adipose tissue, activating thermogenic pathways and increasing energy metabolism. B1R antagonists emerge as promising therapeutic targets for regulating obesity and associated metabolic disorders, such as inflammation and diabetes.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adipose Tissue, Brown
/
Mice, Knockout
/
Thermogenesis
/
Receptor, Bradykinin B1
/
Dioxoles
/
Adipose Tissue, White
Limits:
Animals
Language:
En
Journal:
Inflamm Res
Journal subject:
ALERGIA E IMUNOLOGIA
/
PATOLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Brazil
Country of publication:
Switzerland