Lee Ho Seon, Heo Chan Uk, Song Young-Ho, Lee Kyeong, Choi Chang-Ik
Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, 10326, Goyang, Republic of Korea.
BK21 FOUR Team and Integrated Research Institute for Drug Development, College of Pharmacy, Dongguk University-Seoul, 10326, Goyang, Republic of Korea.
Arch Pharm Res. 2023 Mar;46(3):192-205. doi: 10.1007/s12272-023-01432-7. Epub 2023 Feb 25.
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.
诱导白色脂肪细胞呈现棕色脂肪细胞样表型（脂肪褐变）被认为是治疗肥胖症的一种有前景的治疗策略。柚皮苷是一种柑橘类黄酮，具有抗氧化、抗炎和抗癌活性。基于对其在3T3-L1脂肪细胞中诱导脂肪褐变的研究，我们考察了柚皮苷作为一种抗肥胖化合物的应用情况。柚皮苷不会在分化的3T3-L1脂肪细胞中诱导脂质积累。此外，柚皮苷降低了脂质代谢过程中参与脂肪生成的增殖激活受体γ（PPARγ）和CCAAT/增强子结合蛋白α（C/EBPα）的表达水平，并提高了参与脂肪酸氧化的PPARα和脂联素的水平。脂肪褐变标志物解偶联蛋白1（UCP1；参与产热）和含PR结构域16（PRDM16）的表达水平升高。此外，柚皮苷处理导致PPARγ共激活因子1-α（PGC-1α）活化，PGC-1α是一种与UCP1转录和线粒体生物发生相关的因子。此外，还诱导了米色脂肪细胞特异性基因如Cd137、Cited1、Tbx1和Tmem26的表达。米色脂肪细胞特有的小多脂滴表明，柚皮苷处理提高了所有脂肪分解标志物（激素敏感性脂肪酶[HSL]、脂肪甘油三酯脂肪酶[ATGL]、周脂素[PLIN]和蛋白激酶A[PKA]）的水平。单独用柚皮苷处理可使单磷酸腺苷激活蛋白激酶（AMPK）和UCP1水平升高；这可能是由AMPK信号通路的刺激介导的。根据机制研究，柚皮苷通过AMPK信号通路激活产热蛋白UCP1。总之，柚皮苷可诱导脂肪褐变，基于对脂质代谢的调节，它是一种有前景的治疗代谢紊乱的药物。
