脂肪褐化指的是将白色脂肪细胞诱导成类棕色脂肪细胞，可以成为一种治疗肥胖的有前途的策略。柚皮素是一种柑橘类黄酮，具有抗氧化、抗炎症和抗癌活性。我们研究了柚皮素作为抗肥胖化合物的应用，并针对其诱导 3T3-L1 脂肪细胞中脂肪褐化的机制进行了调查。柚皮素不会诱导分化好的 3T3-L1 脂肪细胞蓄积脂肪。此外，柚皮素降低了参与脂质代谢的脂肪生成激活受体γ（PPARγ）和 CCAAT/增强子结合蛋白α（C/EBPα）的表达水平，增加了参与脂肪酸氧化的 PPARα 和脂联素的水平。脂肪褐化标志物脱耦合蛋白 1（UCP1；参与热原性）和 PR 领域含量 16（PRDM16）的表达水平也增加了。此外，柚皮素处理还导致了与 UCP1 转录和线粒体生物合成有关的 PPARγ 配体结合因子 1-α（PGC-1α）的活化。此外，白色脂肪细胞特异性基因 Cd137、Cited1、Tbx1 和 Tmem26 的表达也被诱导。棕色脂肪细胞的小多脂滴特征表明，柚皮素处理增加了所有脂解标志物（激素敏感性脂解酶[HSL]、脂肪三酯脂肪酶[ATGL]、危险蛋白[PLIN]和蛋白激酶 A[PKA]）的水平。腺苷酸酸性蛋白激酶（AMPK）和 UCP1 水平通过柚皮素治疗单独增加，这可能是通过激活 AMPK 信号通路介导的。根据机制研究，柚皮素通过 AMPK 信号通路激活热原性蛋白 UCP1。总之，柚皮素诱导脂肪褐化，并且能够通过调节脂质代谢成为治疗代谢性疾病的有前途的治疗药物。© 2023. 韩国制药协会。

Induction of the brown adipocyte-like phenotype in white adipocytes (fat browning) is considered a promising therapeutic strategy to treat obesity. Naringin, a citrus flavonoid, has antioxidant, anti-inflammatory, and anticancer activities. We examined the application of naringin as an anti-obesity compound based on an investigation of its induction of fat browning in 3T3-L1 adipocytes. Naringin did not induce lipid accumulation in differentiated 3T3-L1 adipocytes. Additionally, naringin reduced the expression levels of proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) involved in adipogenesis during lipid metabolism and increased the levels of PPARα and adiponectin involved in fatty acid oxidation. The expression levels of fat browning markers uncoupling protein 1 (UCP1; involved in thermogenesis) and PR domain containing 16 (PRDM16) increased. In addition, naringin treatment resulted in the activation of PPARγ coactivator 1-alpha (PGC-1α), a factor related to UCP1 transcription and mitochondrial biogenesis. Moreover, the expression of beige adipocyte-specific genes such as Cd137, Cited1, Tbx1, and Tmem26 was also induced. The small multi-lipid droplets characteristic of beige adipocytes indicated that naringin treatment increased the levels of all lipolysis markers (hormone-sensitive lipase [HSL], adipose triglyceride lipase [ATGL], perilipin [PLIN], and protein kinase A [PKA]). Adenosine monophosphate-activated protein kinase (AMPK) and UCP1 levels increased by treatment with naringin alone; this was possibly mediated by the stimulation of the AMPK signaling pathway. According to mechanistic studies, naringin activated the thermogenic protein UCP1 via the AMPK signaling pathway. In conclusion, naringin induces fat browning and is a promising therapeutic agent for metabolic disorders based on the regulation of lipid metabolism.© 2023. The Pharmaceutical Society of Korea.