Retinaldehyde represses adipogenesis and diet-induced obesity
Retinaldehyde represses adipogenesis and diet-induced obesity
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DOI：
10.1038/nm1587
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发表时间：
2007-06-01
期刊：
影响因子：
82.9
通讯作者：
Plutzky, Jorge
中科院分区：
文献类型：
--
作者：
Ziouzenkova, Ouliana;Orasanu, Gabriela;Plutzky, Jorge
维生素A的代谢及其代谢产物的各种作用受到不同的维甲酸生成酶、维甲酸结合蛋白和维甲酸激活的核受体的严格控制。维甲酸通过激活维甲酸受体和维甲酸X受体(RXR)来调节分化和代谢，间接影响RXR异二聚体。视黄酸完全是由视黄醛(RAD)形成的，而视黄醛又是从维生素A中提取的。目前，视黄酸在眼睛以外的生物作用尚不明确。在这里，我们发现Rald存在于啮齿动物脂肪中，与视黄醇结合蛋白(CRBP1，RBP4)结合，抑制脂肪生成，并抑制过氧化物酶体增殖物激活的受体-c和RXR反应。在体内，缺乏RADD分解酶视黄醛脱氢酶1(Raldh1)的小鼠抵抗饮食诱导的肥胖和胰岛素抵抗，并表现出更多的能量消耗。在ob/ob小鼠中，服用rald或raldh抑制剂可减少脂肪并增加胰岛素敏感性。这些结果确定Rald是对高脂肪饮食的代谢反应的独特的转录调节因子。
The metabolism of vitamin A and the diverse effects of its metabolites are tightly controlled by distinct retinoid-generating enzymes, retinoid-binding proteins and retinoid-activated nuclear receptors. Retinoic acid regulates differentiation and metabolism by activating the retinoic acid receptor and retinoid X receptor (RXR), indirectly influencing RXR heterodimeric partners. Retinoic acid is formed solely from retinaldehyde (Rald), which in turn is derived from vitamin A. Rald currently has no defined biologic role outside the eye. Here we show that Rald is present in rodent fat, binds retinol-binding proteins (CRBP1, RBP4), inhibits adipogenesis and suppresses peroxisome proliferator-activated receptor-c and RXR responses. In vivo, mice lacking the Rald-catabolizing enzyme retinaldehyde dehydrogenase 1 (Raldh1) resisted diet-induced obesity and insulin resistance and showed increased energy dissipation. In ob/ob mice, administrating Rald or a Raldh inhibitor reduced fat and increased insulin sensitivity. These results identify Rald as a distinct transcriptional regulator of the metabolic responses to a high-fat diet.