Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice
Open accessAbstract
Obesity 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.
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BAM15 improves insulin sensitivity and decreases oxidative stress, body adipose tissue mass, hepatic triglyceride accumulation, and inflammatory lipids in diet-induced obese mice.
“Alexopoulus and colleagues273 found that the orally available BAM15, a pH-dependent self-limiting uncoupler, improved insulin sensitivity and decreased oxidative stress, body adipose tissue mass, hepatic triglyceride accumulation and inflammatory lipids in diet-induced obese mice.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [273]
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- Authors
- Alexopoulos, S. J., Chen, S.-Y., Brandon, A. E., Salamoun, J. M., Byrne, F. L., Garcia, C. J., Beretta, M., Olzomer, E. M., Shah, D. P., Philp, A. M., Hargett, S. R., Lawrence, R. T., Lee, B., Sligar, J., Carrive, P., Tucker, S. P., Philp, A., Lackner, C., Turner, N., Cooney, G. J., Santos, W. L., & Hoehn, K. L.
- Affiliations
- UNSW Sydney (AU)
- The University of Sydney (AU)
- Virginia Tech (US)
- Garvan Institute of Medical Research (AU)
- University of Virginia (US)
- Medical University of Graz (AT)
- Corresponding author
- Santos, Webster L.
- Hoehn, Kyle L.
- ORCID
- Alexopoulos, Stephanie J.
- Chen, Sing-Young
- Brandon, Amanda E.
- Byrne, Frances L.
- Garcia, Christopher J.
- Beretta, Martina
- Olzomer, Ellen M.
- Philp, Ashleigh M.
- Hargett, Stefan R.
- Lawrence, Robert T.
- Lee, Brendan
- Sligar, James
- Carrive, Pascal
- Philp, Andrew
- Lackner, Carolin
- Turner, Nigel
- Cooney, Gregory J.
- Santos, Webster L.
- Hoehn, Kyle L.
- Venue
- Nature Communications
- Published
- 2020-05-14
- Volume
- 11
- Issue
- 1
- Pages
- 2397-2397
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC7224297
- OpenAlex
- W3024383047
- Cited by
- 137
- References
- 55
- Citations by year
- 2026: 14 · 2025: 31 · 2024: 17 · 2023: 33 · 2022: 19 · 2021: 17 · 2020: 5
- FWCI
- 11.12
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- VTechWorks (Virginia Tech) (submittedVersion, cc-by)
- Funders
- Virginia Biosciences Health Research Corporation
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- BAM15, mitochondrial uncoupling, diet-induced obesity, insulin resistance, obesity pharmacotherapy, nutrient oxidation, liver fat, antioxidant activity, insulin sensitivity, oral bioavailability, fat mass
- MeSH terms
- Adipose Tissue, Administration, Oral, Animals, Blood Glucose, Body Temperature, Body Weight, Diamines, Disease Models, Animal, Dose-Response Relationship, Drug, Humans, Insulin Resistance, Liver, Male, Mitochondria, Obesity, Oxadiazoles, Pyrazines, Glucose Clamp Technique, Oxidative Stress, Mice, Membrane Potential, Mitochondrial, Diet, Western
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