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Axelrod 2021 EMBO Mol Med - Revision history
2024-03-28T19:42:15Z
Revision history for this page on the wiki
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Plangger Mario at 12:32, 19 July 2021
2021-07-19T12:32:36Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 12:32, 19 July 2021</td>
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<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|abstract=Obesity is a leading cause of preventable death worldwide. Despite this, current strategies for the treatment of obesity remain ineffective at achieving long-term weight control. This is due, in part, to difficulties in identifying tolerable and efficacious small molecules or biologics capable of regulating systemic nutrient homeostasis. Here, we demonstrate that BAM15, a mitochondrially targeted small molecule protonophore, stimulates energy expenditure and glucose and lipid metabolism to protect against diet-induced obesity. Exposure to BAM15 in vitro enhanced mitochondrial respiratory kinetics, improved insulin action, and stimulated nutrient uptake by sustained activation of AMPK. C57BL/6J mice treated with BAM15 were resistant to weight gain. Furthermore, BAM15-treated mice exhibited improved body composition and glycemic control independent of weight loss, effects attributable to drug targeting of lipid-rich tissues. We provide the first phenotypic characterization and demonstration of pre-clinical efficacy for BAM15 as a pharmacological approach for the treatment of obesity and related diseases.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|abstract=Obesity is a leading cause of preventable death worldwide. Despite this, current strategies for the treatment of obesity remain ineffective at achieving long-term weight control. This is due, in part, to difficulties in identifying tolerable and efficacious small molecules or biologics capable of regulating systemic nutrient homeostasis. Here, we demonstrate that BAM15, a mitochondrially targeted small molecule protonophore, stimulates energy expenditure and glucose and lipid metabolism to protect against diet-induced obesity. Exposure to BAM15 <ins style="font-weight: bold; text-decoration: none;">''</ins>in vitro<ins style="font-weight: bold; text-decoration: none;">'' </ins>enhanced mitochondrial respiratory kinetics, improved insulin action, and stimulated nutrient uptake by sustained activation of AMPK. C57BL/6J mice treated with BAM15 were resistant to weight gain. Furthermore, BAM15-treated mice exhibited improved body composition and glycemic control independent of weight loss, effects attributable to drug targeting of lipid-rich tissues. We provide the first phenotypic characterization and demonstration of pre-clinical efficacy for BAM15 as a pharmacological approach for the treatment of obesity and related diseases.</div></td></tr>
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Plangger Mario
https://wiki.oroboros.at/index.php?title=Axelrod_2021_EMBO_Mol_Med&diff=219177&oldid=prev
Reiswig Regina at 12:21, 19 July 2021
2021-07-19T12:21:42Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 12:21, 19 July 2021</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|editor=[[Reiswig R]]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|editor=[[Reiswig R]]</div></td></tr>
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Reiswig Regina
https://wiki.oroboros.at/index.php?title=Axelrod_2021_EMBO_Mol_Med&diff=219176&oldid=prev
Reiswig Regina at 12:20, 19 July 2021
2021-07-19T12:20:41Z
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Reiswig Regina
https://wiki.oroboros.at/index.php?title=Axelrod_2021_EMBO_Mol_Med&diff=219175&oldid=prev
Reiswig Regina at 12:18, 19 July 2021
2021-07-19T12:18:55Z
<p></p>
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 12:18, 19 July 2021</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Axelrod CL, King WT, Davuluri G, Noland RC, Hall J, Hull M, Dantas WS, Zunica ER, Alexopoulos SJ, Hoehn KL, Langohr I, Stadler K, Doyle H, Schmidt E, Nieuwoudt S, Fitzgerald K, Pergola K, Fujioka H, Mey JT, Fealy C, Mulya A, Beyl R, Hoppel CL, Kirwan JP (2021) BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO Mol Med 12:12088.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|title=Axelrod CL, King WT, Davuluri G, Noland RC, Hall J, Hull M, Dantas WS, Zunica ER, Alexopoulos SJ, Hoehn KL, Langohr I, Stadler K, Doyle H, Schmidt E, Nieuwoudt S, Fitzgerald K, Pergola K, Fujioka H, Mey JT, Fealy C, Mulya A, Beyl R, Hoppel CL, Kirwan JP (2021) BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO Mol Med 12:12088.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://pubmed.ncbi.nlm.nih.gov/32519812/ PMID: 32519812 Open Access]</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|info=[https://pubmed.ncbi.nlm.nih.gov/32519812/ PMID: 32519812 Open Access]</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|authors=Christopher L <del style="font-weight: bold; text-decoration: none;">Axelrod</del>, William T <del style="font-weight: bold; text-decoration: none;">King</del>, Gangarao <del style="font-weight: bold; text-decoration: none;">Davuluri</del>, Robert C <del style="font-weight: bold; text-decoration: none;">Noland</del>, Jacob <del style="font-weight: bold; text-decoration: none;">Hall</del>,Michaela <del style="font-weight: bold; text-decoration: none;">Hull</del>, Wagner S <del style="font-weight: bold; text-decoration: none;">Dantas</del>, Elizabeth RM <del style="font-weight: bold; text-decoration: none;">Zunica</del>, Stephanie J <del style="font-weight: bold; text-decoration: none;">Alexopoulos</del>, Kyle L <del style="font-weight: bold; text-decoration: none;">Hoehn</del>,Ingeborg <del style="font-weight: bold; text-decoration: none;">Langohr</del>, Krisztian <del style="font-weight: bold; text-decoration: none;">Stadler</del>, Haylee <del style="font-weight: bold; text-decoration: none;">Doyle</del>, Eva <del style="font-weight: bold; text-decoration: none;">Schmidt</del>, Stephan <del style="font-weight: bold; text-decoration: none;">Nieuwoudt</del>, Kelly <del style="font-weight: bold; text-decoration: none;">Fitzgerald</del>, Kathryn <del style="font-weight: bold; text-decoration: none;">Pergola</del>, Hisashi <del style="font-weight: bold; text-decoration: none;">Fujioka</del>, Jacob T <del style="font-weight: bold; text-decoration: none;">Mey</del>, Ciaran <del style="font-weight: bold; text-decoration: none;">Fealy</del>, Anny <del style="font-weight: bold; text-decoration: none;">Mulya</del>, Robbie <del style="font-weight: bold; text-decoration: none;">Beyl</del>, Charles L <del style="font-weight: bold; text-decoration: none;">Hoppel</del>, John P <del style="font-weight: bold; text-decoration: none;">Kirwan</del></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|authors=<ins style="font-weight: bold; text-decoration: none;">Axelrod </ins>Christopher L, <ins style="font-weight: bold; text-decoration: none;">King </ins>William T, <ins style="font-weight: bold; text-decoration: none;">Davuluri </ins>Gangarao, <ins style="font-weight: bold; text-decoration: none;">Noland </ins>Robert C, <ins style="font-weight: bold; text-decoration: none;">Hall </ins>Jacob, <ins style="font-weight: bold; text-decoration: none;">Hull </ins>Michaela, <ins style="font-weight: bold; text-decoration: none;">Dantas </ins>Wagner S, <ins style="font-weight: bold; text-decoration: none;">Zunica </ins>Elizabeth RM, <ins style="font-weight: bold; text-decoration: none;">Alexopoulos </ins>Stephanie J, <ins style="font-weight: bold; text-decoration: none;">Hoehn </ins>Kyle L, <ins style="font-weight: bold; text-decoration: none;">Langohr </ins>Ingeborg, <ins style="font-weight: bold; text-decoration: none;">Stadler </ins>Krisztian, <ins style="font-weight: bold; text-decoration: none;">Doyle </ins>Haylee, <ins style="font-weight: bold; text-decoration: none;">Schmidt </ins>Eva, <ins style="font-weight: bold; text-decoration: none;">Nieuwoudt </ins>Stephan, <ins style="font-weight: bold; text-decoration: none;">Fitzgerald </ins>Kelly, <ins style="font-weight: bold; text-decoration: none;">Pergola </ins>Kathryn, <ins style="font-weight: bold; text-decoration: none;">Fujioka </ins>Hisashi, <ins style="font-weight: bold; text-decoration: none;">Mey </ins>Jacob T, <ins style="font-weight: bold; text-decoration: none;">Fealy </ins>Ciaran, <ins style="font-weight: bold; text-decoration: none;">Mulya </ins>Anny, <ins style="font-weight: bold; text-decoration: none;">Beyl </ins>Robbie, <ins style="font-weight: bold; text-decoration: none;">Hoppel </ins>Charles L, <ins style="font-weight: bold; text-decoration: none;">Kirwan </ins>John P</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2021</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2021</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=EMBO Mol Med</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|journal=EMBO Mol Med</div></td></tr>
</table>
Reiswig Regina
https://wiki.oroboros.at/index.php?title=Axelrod_2021_EMBO_Mol_Med&diff=219174&oldid=prev
Reiswig Regina: Created page with "{{Publication |title=Axelrod CL, King WT, Davuluri G, Noland RC, Hall J, Hull M, Dantas WS, Zunica ER, Alexopoulos SJ, Hoehn KL, Langohr I, Stadler K, Doyle H, Schmidt E, Nieu..."
2021-07-19T12:13:47Z
<p>Created page with "{{Publication |title=Axelrod CL, King WT, Davuluri G, Noland RC, Hall J, Hull M, Dantas WS, Zunica ER, Alexopoulos SJ, Hoehn KL, Langohr I, Stadler K, Doyle H, Schmidt E, Nieu..."</p>
<p><b>New page</b></p><div>{{Publication<br />
|title=Axelrod CL, King WT, Davuluri G, Noland RC, Hall J, Hull M, Dantas WS, Zunica ER, Alexopoulos SJ, Hoehn KL, Langohr I, Stadler K, Doyle H, Schmidt E, Nieuwoudt S, Fitzgerald K, Pergola K, Fujioka H, Mey JT, Fealy C, Mulya A, Beyl R, Hoppel CL, Kirwan JP (2021) BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO Mol Med 12:12088.<br />
|info=[https://pubmed.ncbi.nlm.nih.gov/32519812/ PMID: 32519812 Open Access]<br />
|authors=Christopher L Axelrod, William T King, Gangarao Davuluri, Robert C Noland, Jacob Hall,Michaela Hull, Wagner S Dantas, Elizabeth RM Zunica, Stephanie J Alexopoulos, Kyle L Hoehn,Ingeborg Langohr, Krisztian Stadler, Haylee Doyle, Eva Schmidt, Stephan Nieuwoudt, Kelly Fitzgerald, Kathryn Pergola, Hisashi Fujioka, Jacob T Mey, Ciaran Fealy, Anny Mulya, Robbie Beyl, Charles L Hoppel, John P Kirwan<br />
|year=2021<br />
|journal=EMBO Mol Med<br />
|abstract=Obesity is a leading cause of preventable death worldwide. Despite this, current strategies for the treatment of obesity remain ineffective at achieving long-term weight control. This is due, in part, to difficulties in identifying tolerable and efficacious small molecules or biologics capable of regulating systemic nutrient homeostasis. Here, we demonstrate that BAM15, a mitochondrially targeted small molecule protonophore, stimulates energy expenditure and glucose and lipid metabolism to protect against diet-induced obesity. Exposure to BAM15 in vitro enhanced mitochondrial respiratory kinetics, improved insulin action, and stimulated nutrient uptake by sustained activation of AMPK. C57BL/6J mice treated with BAM15 were resistant to weight gain. Furthermore, BAM15-treated mice exhibited improved body composition and glycemic control independent of weight loss, effects attributable to drug targeting of lipid-rich tissues. We provide the first phenotypic characterization and demonstration of pre-clinical efficacy for BAM15 as a pharmacological approach for the treatment of obesity and related diseases.<br />
|keywords=AMPK, BAM15, Mitochondria, Obesity, Type 2 diabetes<br />
|editor=[[Reiswig R]]<br />
}}<br />
{{Labeling<br />
|area=Respiration, Pharmacology;toxicology<br />
|organism=Mouse<br />
|tissues=Skeletal muscle<br />
|preparations=Intact cells<br />
|couplingstates=ROUTINE, OXPHOS, ET<br />
|pathways=F, N, S, NS, ROX<br />
|instruments=Oxygraph-2k<br />
|additional=2021-07<br />
}}</div>
Reiswig Regina