Accumulating evidence from both animal and human studies suggests that activation of beige fat increases cellular energy expenditure, ultimately reducing adiposity. Here, we report the central role of adipocyte-derived lysyl oxidase (Lox) in the formation of thermogenic beige fat. Mice exposed to cold or a β3 agonist showed drastically lower Lox expression in thermogenically activated beige fat. Importantly, inhibition of Lox activity with BAPN stimulated biogenesis of beige fat in inguinal white adipose tissue (iWAT) under housing conditions and potentiated cold-induced adaptive thermogenesis and beiging in both iWAT and epididymal white adipose tissue (eWAT). Notably, white adipocytes with Lox repression undergo transdifferentiation into beige adipocytes which can be suppressed by tumor necrosis factor-α (TNFα) via ERK activation. This work provides new insight into the molecular control to expand beige fat by Lox inhibition and suggest the potential for utilizing inhibitor of Lox to treat the emerging epidemics of obesity and diabetes.

来自动物和人类研究的越来越多的证据表明，米色脂肪的激活会增加细胞能量消耗，最终减少肥胖。在这里，我们报告了脂肪细胞衍生的赖氨酰氧化酶 (Lox) 在产热米色脂肪形成中的核心作用。暴露于寒冷或 β3 激动剂的小鼠在产热激活的米色脂肪中表现出显着降低的 Lox 表达。重要的是，在住房条件下，用 BAPN 抑制 Lox 活性会刺激腹股沟白色脂肪组织 (iWAT) 中米色脂肪的生物生成，并增强 iWAT 和附睾白色脂肪组织 (eWAT) 中冷诱导的适应性产热和米色。值得注意的是，具有 Lox 抑制的白色脂肪细胞经历转分化为米色脂肪细胞，这可以通过 ERK 激活被肿瘤坏死因子-α (TNFα) 抑制。