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

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 (LTB 4 ), 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 LTB 4 /BLT1 axis. These results indicate that LTA 4 H mediates the diet‐induced obesity by reducing catecholamine and thyroid hormone secretion.