Steen Jakobsen

Metformin Targets Brown Adipose Tissue in vivo and Reduces Oxygen Consumption in vitro

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DOI

Metformin is the most widely prescribed oral antidiabetic drug worldwide. Despite well-documented beneficial effects on health outcomes in diabetic patients, the target organs that mediate the effects of metformin remain to be established. In adult humans, brown adipose tissue (BAT) can influence basic metabolic rate, making BAT an attractive target for treatment of type 2 diabetes. Under the hypothesis that BAT is a metformin target tissue, we investigated in vivo uptake of [11 C]-metformin tracer in mice and studied in vitro effects of metformin on cultured human brown adipocytes. Injected [11 C]-metformin revealed avid uptake in the murine interscapular BAT depot. Metformin exposure in BAT was comparable 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. Collectively, these results support BAT as a putative metformin target. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalDiabetes, Obesity and Metabolism
Volume20
Issue9
Pages (from-to)2264-2273
ISSN1462-8902
DOIs
Publication statusPublished - Sep 2018

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