Remodelling of energy storing white fat into energy expending beige fat could be a promising strategy to reduce adiposity. Here, we show that the bile acid-responsive membrane receptor TGR5 mediates beiging of the subcutaneous white adipose tissue (scWAT) under multiple environmental cues including cold exposure and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective bile acid mimetics to thermoneutral housed mice leads to the appearance of beige adipocyte markers and increases mitochondrial content in the scWAT of Tgr5 ^+/+ mice but not in their Tgr5 ^-/- littermates. This phenotype is recapitulated in vitro in differentiated adipocytes, in which TGR5 activation increases free fatty acid availability through lipolysis, hence fuelling β-oxidation and thermogenic activity. TGR5 signalling also induces mitochondrial fission through the ERK/DRP1 pathway, further improving mitochondrial respiration. Taken together, these data identify TGR5 as a druggable target to promote beiging with potential applications in the management of metabolic disorders.

中文翻译：

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TGR5信号传导促进白色脂肪组织的线粒体裂变和米色重塑。

将能量储存的白色脂肪重塑成消耗米色脂肪的能量可能是减少肥胖的有前途的策略。在这里，我们显示胆汁酸反应膜受体TGR5介导皮下白色脂肪组织（scWAT）的乞讨在多种环境提示下，包括冷暴露和长期高脂饮食喂养。此外，将TGR5选择性胆汁酸模拟物给予热中性笼养小鼠会导致米色脂肪细胞标志物的出现，并增加Tgr5 ^{+ / +}小鼠的scWAT中的线粒体含量，但不会增加其Tgr5 ^-/-的线粒体含量同窝仔。该表型在体外在分化的脂肪细胞中概括，其中TGR5活化通过脂解作用增加了游离脂肪酸的利用率，从而加剧了β-氧化作用和产热活性。TGR5信号转导也通过ERK / DRP1途径诱导线粒体分裂，从而进一步改善线粒体呼吸。综上所述，这些数据将TGR5鉴定为可药物化的靶标，以促进在代谢障碍管理中的潜在应用。