Weight loss by Ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold.
Weight loss by Ppc-1, a novel small molecule mitochondrial uncoupler derived from slime mold.
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DOI：
10.1371/journal.pone.0117088
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Homma Y
中科院分区：
文献类型：
--
作者：
Suzuki T;Kikuchi H;Ogura M;Homma MK;Oshima Y;Homma Y
线粒体在包括ATP合成和细胞凋亡在内的多种过程中发挥关键作用。线粒体功能可以使用呼吸抑制剂进行研究，新的药物对发现线粒体调节的新机制很有价值。在这里，我们筛选了来自黏菌和其他微生物的小分子对线粒体耗氧量的影响。我们确定Ppc-1作为一种新的分子，刺激氧的消耗，而不会对ATP的生产产生不利影响。Ppc-1的动力学行为表明其作为线粒体解偶联剂的功能。连续给予小鼠Ppc-1抑制了体重增加，对肝脏或肾脏组织没有异常影响，也没有肿瘤形成的证据。在用Ppc-1处理的小鼠中，血清脂肪酸水平显著升高，而体脂含量保持较低。单次给药后，Ppc-1以低水平分布到个体动物的各种组织中。PPC-1刺激培养中的脂肪细胞释放脂肪酸，这可能解释PPC-1治疗小鼠血清脂肪酸升高的原因。结果表明，PPC-1是一种独特的线粒体调节因子，这将是线粒体研究以及开发治疗肥胖新药的有价值的工具。
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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影响因子：
2.4
作者：
Kubohara Y;Kikuchi H;Matsuo Y;Oshima Y;Homma Y
通讯作者：
Homma Y
影响因子：
5.5
作者：
Kabuyama, Yukihito;Suzuki, Toshiyuki;Homma, Yoshimi
通讯作者：
Homma, Yoshimi
影响因子：
2.9
作者：
HEYTLER, PG
通讯作者：
HEYTLER, PG
影响因子：
4.1
作者：
MORRIS, HR;MASENTO, MS;KAY, RR
通讯作者：
KAY, RR
DOI：
10.1006/bbrc.1997.6964
发表时间：
1997-07-18
影响因子：
3.1
作者：
Kubohara, Y
通讯作者：
Kubohara, Y