Naringin promotes fat browning mediated by UCP1 activation via the AMPK signaling pathway in 3T3-L1 adipocytes

IF 6.9 3区 医学 Q1 CHEMISTRY, MEDICINAL Archives of Pharmacal Research Pub Date : 2023-02-25 DOI:10.1007/s12272-023-01432-7
Ho Seon Lee, Chan Uk Heo,  Young-Ho Song, Kyeong Lee, Chang-Ik Choi
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引用次数: 2

Abstract

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.

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柚皮苷通过AMPK信号通路促进3T3-L1脂肪细胞中UCP1激活介导的脂肪褐变
在白色脂肪细胞中诱导棕色脂肪细胞样表型(脂肪褐变)被认为是治疗肥胖的一种有前途的治疗策略。柚皮苷是一种柑橘类黄酮,具有抗氧化、抗炎和抗癌活性。我们在研究柚皮苷诱导3T3-L1脂肪细胞脂肪褐变的基础上,探讨了柚皮苷作为抗肥胖化合物的应用。柚皮苷不诱导分化的3T3-L1脂肪细胞的脂质积累。此外,柚皮素降低脂质代谢过程中参与脂肪形成的增殖因子激活受体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;PR结构域16 (PRDM16)表达增加。此外,柚皮苷处理导致PPARγ共激活因子1- α (PGC-1α)的激活,这是一个与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Cd137、Cited1、Tbx1和Tmem26的表达。米色脂肪细胞的小多脂滴特征表明,柚皮苷处理增加了所有脂解标志物(激素敏感脂肪酶[HSL]、脂肪甘油三酯脂肪酶[ATGL]、佩里平[PLIN]和蛋白激酶A [PKA])的水平。单磷酸腺苷活化蛋白激酶(AMPK)和UCP1水平升高;这可能是通过刺激AMPK信号通路介导的。根据机制研究,柚皮苷通过AMPK信号通路激活产热蛋白UCP1。综上所述,柚皮苷可诱导脂肪褐变,是一种很有前景的基于脂质代谢调节的代谢紊乱药物。
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来源期刊
CiteScore
13.40
自引率
9.00%
发文量
48
审稿时长
3.3 months
期刊介绍: Archives of Pharmacal Research is the official journal of the Pharmaceutical Society of Korea and has been published since 1976. Archives of Pharmacal Research is an interdisciplinary journal devoted to the publication of original scientific research papers and reviews in the fields of drug discovery, drug development, and drug actions with a view to providing fundamental and novel information on drugs and drug candidates.
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