Pharmacological inhibition of ALDH1A enzymes suppresses weight gain in a mouse model of diet-induced obesity.
Pharmacological inhibition of ALDH1A enzymes suppresses weight gain in a mouse model of diet-induced obesity.
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DOI：
10.1016/j.orcp.2017.08.003
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发表时间：
2018-01
影响因子：
4.3
通讯作者：
Paik J
中科院分区：
文献类型：
--
作者：
Haenisch M;Treuting PM;Brabb T;Goldstein AS;Berkseth K;Amory JK;Paik J
已知视黄酸 (RA) 在体重调节中发挥作用。由于缺乏 ALDH1A1（一种主要的 RA 合成酶）的小鼠对饮食诱导的肥胖具有抵抗力，因此我们测试了一个假设，即药物抑制 RA 合成可以在饮食诱导的肥胖小鼠模型中抑制体重增加。 C57BL/6J 雄性小鼠被喂食高脂肪饮食 (HFD) 8 周以诱导肥胖，然后随机接受含或不含 WIN 18,446（一种 RA 合成抑制剂）的 HFD 组，再持续 9 周。测量体重、身体成分、能量消耗、活动和食物摄入量。还测定了类维生素A、脂质以及参与类维生素A和脂质代谢的基因的水平。用 WIN 18,446 治疗的小鼠体重明显减轻，并且脂肪组织重量、脂肪细胞大小和脂肪组织中的巨噬细胞浸润减少。此外，我们观察到接受 WIN 18,446 治疗的小鼠脂肪组织中 UCP1 表达较高，而肝脏和肺中 RA 反应基因和参与脂肪酸合成的基因表达降低。因此，通过抑制 ALDH1A1 来抑制 RA 合成可能是治疗肥胖症的潜在新靶点。
Retinoic acid (RA) is known to play a role in weight regulation. Because mice without ALDH1A1, a major RA synthesizing enzyme, are resistant to diet-induced obesity, we tested a hypothesis that pharmacological inhibition of RA synthesis can suppress weight gain in a murine model of diet-induced obesity. C57BL/6J male mice were fed a high fat diet (HFD) for 8 weeks to induce obesity and then randomized to a HFD with or without WIN 18,446, an RA synthesis inhibitor, for an additional 9 weeks. Body weight, body composition, energy expenditure, activity, and food intake were measured. Levels of retinoids, lipids, and genes involved in the metabolism of retinoid and lipids were also determined. Mice treated with WIN 18,446 gained significantly less weight and had decreased adipose tissue weight, adipocyte size, and macrophage infiltration in adipose tissue. In addition, we observed higher UCP1 expression in adipose tissues and decreased expression of RA responsive genes and genes involved in fatty acid synthesis in the livers and lungs of mice treated with WIN 18,446. Thus, pharmacological suppression of RA synthesis via inhibition of ALDH1A1 may be a potential new target for treatment of obesity.
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视网膜甲醛脱氢酶1调节白色脂肪组织中的热程序。
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
5.1
作者：
Moreb, Jan S.;Ucar, Deniz;Han, Shuhong;Amory, John K.;Goldstein, Alex S.;Ostmark, Blanca;Chang, Lung-Ji
通讯作者：
Chang, Lung-Ji
影响因子：
4.8
作者：
Kiefer, Florian W.;Orasanu, Gabriela;Plutzky, Jorge
通讯作者：
Plutzky, Jorge
影响因子：
82.9
作者：
Ziouzenkova, Ouliana;Orasanu, Gabriela;Plutzky, Jorge
通讯作者：
Plutzky, Jorge
对于不同的热条件，食物摄入量的自适应变化（而不是能量消耗）需要瘦素信号传导。
影响因子：
3.7
作者：
Kaiyala KJ;Ogimoto K;Nelson JT;Schwartz MW;Morton GJ
通讯作者：
Morton GJ