Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro.
Diabetes Obes Metab
; 20(9): 2264-2273, 2018 09.
Article
in En
| MEDLINE
| ID: mdl-29752759
ABSTRACT
AIMS:
To test the hypothesis that brown adipose tissue (BAT) is a metformin target tissue by investigating in vivo uptake of [11 C]-metformin tracer in mice and studying in vitro effects of metformin on cultured human brown adipocytes. MATERIALS ANDMETHODS:
Tissue-specific uptake of metformin was assessed in mice by PET/CT imaging after injection of [11 C]-metformin. Human brown adipose tissue was obtained from elective neck surgery and metformin transporter expression levels in human and murine BAT were determined by qPCR. Oxygen consumption in metformin-treated human brown adipocyte cell models was assessed by Seahorse XF technology.RESULTS:
Injected [11 C]-metformin showed avid uptake in the murine interscapular BAT depot. Metformin exposure in BAT was similar to hepatic exposure. Non-specific inhibition of the organic cation transporter (OCT) protein by cimetidine administration eliminated BAT exposure to metformin, demonstrating OCT-mediated uptake. Gene expression profiles of OCTs in BAT revealed ample OCT3 expression in both human and mouse BAT. Incubation of a human brown adipocyte cell models with metformin reduced cellular oxygen consumption in a dose-dependent manner.CONCLUSION:
These results support BAT as a putative metformin target.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxygen Consumption
/
Adipose Tissue, Brown
/
Hypoglycemic Agents
/
Metformin
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Diabetes Obes Metab
Journal subject:
ENDOCRINOLOGIA
/
METABOLISMO
Year:
2018
Document type:
Article
Affiliation country:
Denmark