title: Weight loss by Ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold.
abstract: 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.
authors: Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.
authors: Toshiyuki
authors: T
authors: Suzuki
authors: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8678, Japan.
authors: Haruhisa
authors: H
authors: Kikuchi
authors: Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.
authors: Masato
authors: M
authors: Ogura
authors: Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.
authors: Miwako K
authors: MK
authors: Homma
authors: Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, 980-8678, Japan.
authors: Yoshiteru
authors: Y
authors: Oshima
authors: Fukushima Medical University School of Medicine, Fukushima, 960-1295, Japan.
authors: Yoshimi
authors: Y
authors: Homma
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D016837:Dictyosteliida / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D054852:Small Molecule Libraries / Q000494:pharmacology*; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D005227:Fatty Acids; D054852:Small Molecule Libraries; D000255:Adenosine Triphosphate