Premium
Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro
Author(s) -
Breining Peter,
Jensen Jonas B.,
Sundelin Elias I.,
Gormsen Lars C.,
Jakobsen Steen,
Busk Morten,
Rolighed Lars,
Bross Peter,
FernandezGuerra Paula,
Markussen Lasse K.,
Rasmussen Nanna E.,
Hansen Jacob B.,
Pedersen Steen B.,
Richelsen Bjørn,
Jessen Niels
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13362
Subject(s) - metformin , in vivo , organic cation transport proteins , adipose tissue , brown adipose tissue , adipocyte , endocrinology , medicine , biology , pharmacology , glucose uptake , chemistry , transporter , diabetes mellitus , biochemistry , insulin , gene , microbiology and biotechnology
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 and methods 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.