Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice

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dc.contributor.authorAlexopoulos, Stephanie J.en
dc.contributor.authorChen, Sing-Youngen
dc.contributor.authorBrandon, Amanda E.en
dc.contributor.authorSalamoun, Joseph M.en
dc.contributor.authorByrne, Frances L.en
dc.contributor.authorGarcia, Christopher J.en
dc.contributor.authorBeretta, Martinaen
dc.contributor.authorOlzomer, Ellen M.en
dc.contributor.authorShah, Divya P.en
dc.contributor.authorPhilp, Ashleigh M.en
dc.contributor.authorHargett, Stefan R.en
dc.contributor.authorLawrence, Robert T.en
dc.contributor.authorLee, Brendanen
dc.contributor.authorSligar, Jamesen
dc.contributor.authorCarrive, Pascalen
dc.contributor.authorTucker, Simon P.en
dc.contributor.authorPhilp, Andrewen
dc.contributor.authorLackner, Carolinen
dc.contributor.authorTurner, Nigelen
dc.contributor.authorCooney, Gregory J.en
dc.contributor.authorSantos, Webster L.en
dc.contributor.authorHoehn, Kyle L.en
dc.contributor.departmentChemistryen
dc.date.accessioned2020-06-08T14:44:39Zen
dc.date.available2020-06-08T14:44:39Zen
dc.date.issued2020-05-14en
dc.description.abstractObesity is a health problem affecting more than 40% of US adults and 13% of the global population. Anti-obesity treatments including diet, exercise, surgery and pharmacotherapies have so far failed to reverse obesity incidence. Herein, we target obesity with a pharmacotherapeutic approach that decreases caloric efficiency by mitochondrial uncoupling. We show that a recently identified mitochondrial uncoupler BAM15 is orally bioavailable, increases nutrient oxidation, and decreases body fat mass without altering food intake, lean body mass, body temperature, or biochemical and haematological markers of toxicity. BAM15 decreases hepatic fat, decreases inflammatory lipids, and has strong antioxidant effects. Hyperinsulinemic-euglycemic clamp studies show that BAM15 improves insulin sensitivity in multiple tissue types. Collectively, these data demonstrate that pharmacologic mitochondrial uncoupling with BAM15 has powerful anti-obesity and insulin sensitizing effects without compromising lean mass or affecting food intake.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41467-020-16298-2en
dc.identifier.urihttp://hdl.handle.net/10919/98778en
dc.identifier.volume11en
dc.language.isoenen
dc.publisherNature Researchen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleMitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in miceen
dc.title.serialNature Communicationsen
dc.typeArticle - Refereeden

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