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Weight Loss by Ppc-1, a Novel Small Molecule Mitochondrial Uncoupler Derived from Slime Mold

Mitochondria play a key role in diverse processes including ATP synthesis and apoptosis. Mitochondrial function can be studied using inhibitors of respiration, and new agents are valuable for discovering novel mechanisms involved in mitochondrial regulation. Here, we screened small molecules derived...

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Detalles Bibliográficos
Autores principales: Suzuki, Toshiyuki, Kikuchi, Haruhisa, Ogura, Masato, Homma, Miwako K., Oshima, Yoshiteru, Homma, Yoshimi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323345/
https://www.ncbi.nlm.nih.gov/pubmed/25668511
http://dx.doi.org/10.1371/journal.pone.0117088
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author Suzuki, Toshiyuki
Kikuchi, Haruhisa
Ogura, Masato
Homma, Miwako K.
Oshima, Yoshiteru
Homma, Yoshimi
author_facet Suzuki, Toshiyuki
Kikuchi, Haruhisa
Ogura, Masato
Homma, Miwako K.
Oshima, Yoshiteru
Homma, Yoshimi
author_sort Suzuki, Toshiyuki
collection PubMed
description Mitochondria play a key role in diverse processes including ATP synthesis and apoptosis. Mitochondrial function can be studied using inhibitors of respiration, and new agents are valuable for discovering novel mechanisms involved in mitochondrial regulation. Here, we screened small molecules derived from slime molds and other microorganisms for their effects on mitochondrial oxygen consumption. We identified Ppc-1 as a novel molecule which stimulates oxygen consumption without adverse effects on ATP production. The kinetic behavior of Ppc-1 suggests its function as a mitochondrial uncoupler. Serial administration of Ppc-1 into mice suppressed weight gain with no abnormal effects on liver or kidney tissues, and no evidence of tumor formation. Serum fatty acid levels were significantly elevated in mice treated with Ppc-1, while body fat content remained low. After a single administration, Ppc-1 distributes into various tissues of individual animals at low levels. Ppc-1 stimulates adipocytes in culture to release fatty acids, which might explain the elevated serum fatty acids in Ppc-1-treated mice. The results suggest that Ppc-1 is a unique mitochondrial regulator which will be a valuable tool for mitochondrial research as well as the development of new drugs to treat obesity.
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spelling pubmed-43233452015-02-18 Weight Loss by Ppc-1, a Novel Small Molecule Mitochondrial Uncoupler Derived from Slime Mold Suzuki, Toshiyuki Kikuchi, Haruhisa Ogura, Masato Homma, Miwako K. Oshima, Yoshiteru Homma, Yoshimi PLoS One Research Article Mitochondria play a key role in diverse processes including ATP synthesis and apoptosis. Mitochondrial function can be studied using inhibitors of respiration, and new agents are valuable for discovering novel mechanisms involved in mitochondrial regulation. Here, we screened small molecules derived from slime molds and other microorganisms for their effects on mitochondrial oxygen consumption. We identified Ppc-1 as a novel molecule which stimulates oxygen consumption without adverse effects on ATP production. The kinetic behavior of Ppc-1 suggests its function as a mitochondrial uncoupler. Serial administration of Ppc-1 into mice suppressed weight gain with no abnormal effects on liver or kidney tissues, and no evidence of tumor formation. Serum fatty acid levels were significantly elevated in mice treated with Ppc-1, while body fat content remained low. After a single administration, Ppc-1 distributes into various tissues of individual animals at low levels. Ppc-1 stimulates adipocytes in culture to release fatty acids, which might explain the elevated serum fatty acids in Ppc-1-treated mice. The results suggest that Ppc-1 is a unique mitochondrial regulator which will be a valuable tool for mitochondrial research as well as the development of new drugs to treat obesity. Public Library of Science 2015-02-10 /pmc/articles/PMC4323345/ /pubmed/25668511 http://dx.doi.org/10.1371/journal.pone.0117088 Text en © 2015 Suzuki et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Suzuki, Toshiyuki
Kikuchi, Haruhisa
Ogura, Masato
Homma, Miwako K.
Oshima, Yoshiteru
Homma, Yoshimi
Weight Loss by Ppc-1, a Novel Small Molecule Mitochondrial Uncoupler Derived from Slime Mold
title Weight Loss by Ppc-1, a Novel Small Molecule Mitochondrial Uncoupler Derived from Slime Mold
title_full Weight Loss by Ppc-1, a Novel Small Molecule Mitochondrial Uncoupler Derived from Slime Mold
title_fullStr Weight Loss by Ppc-1, a Novel Small Molecule Mitochondrial Uncoupler Derived from Slime Mold
title_full_unstemmed Weight Loss by Ppc-1, a Novel Small Molecule Mitochondrial Uncoupler Derived from Slime Mold
title_short Weight Loss by Ppc-1, a Novel Small Molecule Mitochondrial Uncoupler Derived from Slime Mold
title_sort weight loss by ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4323345/
https://www.ncbi.nlm.nih.gov/pubmed/25668511
http://dx.doi.org/10.1371/journal.pone.0117088
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