Cargando…
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...
Autores principales: | , , , , , |
---|---|
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 |
_version_ | 1782356534827679744 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4323345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT suzukitoshiyuki weightlossbyppc1anovelsmallmoleculemitochondrialuncouplerderivedfromslimemold AT kikuchiharuhisa weightlossbyppc1anovelsmallmoleculemitochondrialuncouplerderivedfromslimemold AT oguramasato weightlossbyppc1anovelsmallmoleculemitochondrialuncouplerderivedfromslimemold AT hommamiwakok weightlossbyppc1anovelsmallmoleculemitochondrialuncouplerderivedfromslimemold AT oshimayoshiteru weightlossbyppc1anovelsmallmoleculemitochondrialuncouplerderivedfromslimemold AT hommayoshimi weightlossbyppc1anovelsmallmoleculemitochondrialuncouplerderivedfromslimemold |