Leukotriene A4 hydrolase deficiency protects mice from diet-induced obesity by increasing energy expenditure through neuroendocrine axis.
Leukotriene A4 hydrolase deficiency protects mice from diet-induced obesity by increasing energy expenditure through neuroendocrine axis.
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白三烯 A4 水解酶缺乏症通过神经内分泌轴增加能量消耗，从而保护小鼠免受饮食引起的肥胖。
DOI：
10.1096/fj.202001148r
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发表时间：
2020
期刊：
影响因子：
4.8
通讯作者：
Yokomizo T
中科院分区：
文献类型：
--
作者：
Uzawa H;Kohno D;Koga T;Sasaki T;Fukunaka A;Okuno T;Jo-Watanabe A;Kazuno S;Miyatsuka T;Kitamura T;Fujitani Y;Watada H;Saeki K*;Yokomizo T
肥胖是一个世界性的健康问题，棕色脂肪组织(BAT)对能量消耗很重要。在这里，我们探讨了白三烯A4水解酶(LTA4H)在饮食诱导的肥胖中的作用，白三烯A4水解酶是合成脂质介质白三烯B4(LTB4)的关键酶。LTA4H缺陷型(LTA4H-KO)小鼠在高脂饮食(HFD)中表现出瘦削41的表型，骨髓移植研究表明42个非造血细胞中的LTA4H缺乏是导致这种瘦削表型的原因。LTA4H-KO小鼠43表现出更大的能量消耗，但食物摄入量和粪便能量损失相似。LTA4H-44KO BAT产热相关基因表达水平较高。此外，LTA4H-KO小鼠血浆中45种促甲状腺激素和甲状腺激素浓度以及HFD诱导的46种儿茶酚胺的分泌量都较高。相比之下，LTB4受体47(BLT1)缺陷小鼠没有表现出瘦削的表型，这意味着48只LTA4H-KO小鼠的表型与LTB4/BLT1轴无关。这些结果表明，LTA4H49通过减少儿茶酚胺和甲状腺激素的分泌来调节饮食诱导的肥胖。50 51
Obesity is a health problem worldwide, and brown adipose tissue (BAT) is important for 38 energy expenditure. Here, we explored the role of leukotriene A4 hydrolase (LTA4H), a key 39 enzyme in the synthesis of the lipid mediator leukotriene B4 (LTB4), in diet-induced 40 obesity. LTA4H-deficient (LTA4H-KO) mice fed a high-fat diet (HFD) showed a lean 41 phenotype, and bone-marrow transplantation studies revealed that LTA4H-deficiency in 42 non-hematopoietic cells was responsible for this lean phenotype. LTA4H-KO mice 43 exhibited greater energy expenditure, but similar food intake and fecal energy loss. LTA4H-44 KO BAT showed higher expression of thermogenesis-related genes. In addition, the plasma 45 thyroid-stimulating hormone and thyroid hormone concentrations, as well as HFD-induced 46 catecholamine secretion, were higher in LTA4H-KO mice. By contrast, LTB4 receptor 47 (BLT1)-deficient mice did not show a lean phenotype, implying that the phenotype of 48 LTA4H-KO mice is independent of the LTB4/BLT1 axis. These results indicate that LTA4H 49 mediates diet-induced obesity by reducing catecholamine and thyroid hormone secretion. 50 51