Metformin targets brown adipose tissue in vivo and reduces oxygen consumption in vitro

Diabetes, Obesity & Metabolism
Peter BreiningN Jessen

Abstract

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. 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. 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. These results support BAT as a putative metformin target.

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Citations

Feb 6, 2020·Canadian Journal of Physiology and Pharmacology·Hacene BourasJoost G J Hoenderop
Sep 23, 2018·International Journal of Molecular Sciences·Joseph ZhouLixin Li
May 20, 2020·Frontiers in Endocrinology·Ziquan Lv, Yajie Guo
Dec 20, 2019·Pharmacological Reviews·Hermann Koepsell
Dec 4, 2019·Diabetology & Metabolic Syndrome·Tao YuanZhu-Fang Shen
May 5, 2020·Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Métabolisme·Flávia R OliveiraFernando M Reis
Nov 10, 2020·Expert Review of Neurotherapeutics·Sarah DemaréPaul Fernyhough
May 15, 2021·Molecular and Cellular Endocrinology·Jessica M Hoffman, Teresa G Valencak
Jun 3, 2021·International Journal of Molecular Sciences·Tiago MoraisMariana P Monteiro
Jul 3, 2021·International Journal of Molecular Sciences·Isabella PanfoliDavide Maggi

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