Obesity contributes to the progression of various chronic diseases, and shortens life expectancy. With abundant mitochondria, brown adipose tissue (BAT) dissipates energy through heat to limit weight gain and metabolic dysfunction in obesity. Our previous studies have shown that aurantio-obtusin (AO), a bioactive ingredient in Chinese traditional medicine Cassiae semen significantly improves hepatic lipid metabolism in a steatotic mouse model. In the current study we investigated the effects of AO on lipid metabolism in the BAT of diet-induced obesity mice and in oleic acid and palmitic acid (OAPA)-stimulated primary mature BAT adipocytes. Obese mice were established by feeding a HFHS diet for 4 weeks, and then administered AO (10 mg/kg, i.g.) for another 4 weeks. We showed that AO administration significantly increased the weight of BAT and accelerated energy expenditure to protect the weight increase in the obese mice. Using RNA sequencing and molecular biology analysis we found that AO significantly enhanced mitochondrial metabolism and UCP1 expression by activating PPARα both in vivo and in vitro in the primary BAT adipocytes. Interestingly, AO administration did not improve metabolic dysfunction in the liver and white adipose tissue of obese mice after interscapular BAT excision. We demonstrated that low temperature, a trigger of BAT thermogenesis, was not a decisive factor for AO to stimulate the growth and activation of BATs. This study uncovers a regulatory network of AO in activating BAT-dependent lipid consumption and brings up a new avenue for the pharmaceutical intervention in obesity and related comorbidities.

肥胖会导致各种慢性疾病的进展，并缩短预期寿命。棕色脂肪组织 (BAT) 具有丰富的线粒体，通过热量耗散能量，以限制肥胖引起的体重增加和代谢功能障碍。我们前期的研究表明，中药决明子中的生物活性成分金黄素（AO）可显着改善脂肪变性小鼠模型的肝脏脂质代谢。在当前的研究中，我们研究了 AO 对饮食诱导的肥胖小鼠 BAT 以及油酸和棕榈酸 (OAPA) 刺激的初级成熟 BAT 脂肪细胞中脂质代谢的影响。通过喂养 HFHS 饮食 4 周，然后再施用 AO（10 mg/kg，ig）4 周来建立肥胖小鼠。我们发现，AO 给药显着增加了 BAT 的重量并加速了能量消耗，从而保护了肥胖小鼠的体重增加。通过RNA测序和分子生物学分析，我们发现AO通过在体内和体外激活原代BAT脂肪细胞中的PPARα来显着增强线粒体代谢和UCP1表达。有趣的是，AO 给药并没有改善肥胖小鼠肩胛间 BAT 切除后肝脏和白色脂肪组织的代谢功能障碍。我们证明，低温作为 BAT 生热作用的触发因素，并不是 AO 刺激 BAT 生长和激活的决定性因素。这项研究揭示了 AO 在激活 BAT 依赖性脂质消耗中的调节网络，并为肥胖和相关合并症的药物干预提供了新途径。