Shan Jiang, Taolin Yuan, Florian A Rosenberger, Arnaud Mourier, Nathalia R V Dragano, Laura S Kremer, Diana Rubalcava-Gracia, Fynn M Hansen, Melissa Borg, Mara Mennuni, Roberta Filograna, David Alsina, Jelena Misic, Camilla Koolmeister, Polyxeni Papadea, Martin Hrabe de Angelis, Lipeng Ren, Olov Andersson, Anke Unger, Tim Bergbrede, Raffaella Di Lucrezia, Rolf Wibom, Juleen R Zierath, Anna Krook, Patrick Giavalisco, Matthias Mann, Nils-Göran Larsson
The oxidative phosphorylation system1 in mammalian mitochondria plays a key role in transducing energy from ingested nutrients2 . Mitochondrial metabolism is dynamic and can be reprogrammed to support both catabolic and anabolic reactions, depending on physiological demands or disease states. Rewiring of mitochondrial metabolism is intricately linked to metabolic diseases and promotes tumour growth3-5 . Here, we demonstrate that oral treatment with an inhibitor of mitochondrial transcription (IMT)6 shifts whole-animal metabolism towards fatty acid oxidation, which, in turn, leads to rapid normalization of body weight, reversal of hepatosteatosis and restoration of normal glucose tolerance in male mice on a high-fat diet...
April 30, 2024: Nature metabolism