Leukotriene A(4)hydrolase deficiency protects mice from diet-induced obesity by increasing energy expenditure through neuroendocrine axis

Article

关键词: BROWN ADIPOSE-TISSUE;    BIFUNCTIONAL ENZYME;    INSULIN-RESISTANCE;    B-4 RECEPTOR;    ACTIVE-SITE;    HYDROLASE;    AMINOPEPTIDASE;    IDENTIFICATION;    THERMOGENESIS;    LTA(4)H;   

DOI  :  10.1096/fj.202001148R

来源: SCIE

【 摘 要 】

Obesity is a health problem worldwide, and brown adipose tissue (BAT) is important for energy expenditure. Here, we explored the role of leukotriene A(4)hydrolase (LTA(4)H), a key enzyme in the synthesis of the lipid mediator leukotriene B-4(LTB4), in diet-induced obesity. LTA(4)H-deficient (LTA(4)H-KO) mice fed a high-fat diet (HFD) showed a lean phenotype, and bone-marrow transplantation studies revealed that LTA(4)H-deficiency in non-hematopoietic cells was responsible for this lean phenotype. LTA(4)H-KO mice exhibited greater energy expenditure, but similar food intake and fecal energy loss. LTA(4)H-KO BAT showed higher expression of thermogenesis-related genes. In addition, the plasma thyroid-stimulating hormone and thyroid hormone concentrations, as well as HFD-induced catecholamine secretion, were higher in LTA(4)H-KO mice. In contrast, LTB(4)receptor (BLT1)-deficient mice did not show a lean phenotype, implying that the phenotype of LTA(4)H-KO mice is independent of the LTB4/BLT1 axis. These results indicate that LTA(4)H mediates the diet-induced obesity by reducing catecholamine and thyroid hormone secretion.

【 授权许可】

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