Buddhist Tzu Chi Bioinnovation Center, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan.
Department of Medical Research, Hualien Tzu Chi Hospital, Hualien 970, Taiwan.
Biochim Biophys Acta Mol Cell Biol Lipids. 2021 Dec;1866(12):159033. doi: 10.1016/j.bbalip.2021.159033. Epub 2021 Sep 3.
Thermogenesis (non-exercise activity) in brown adipose tissue (BAT) promotes energy expenditure because of its higher number of mitochondria than white adipose tissue (WAT). The main function of thermogenesis in BAT can counteract obesity through the dissipation of calories as heat. N-butylidenephthalide (BP) is a natural derivative from Angelica sinensis, a Chinese herb that has been used for thousands of years. In this report, we demonstrated that BP improved the metabolic profiles of mice with high fat diet-induced obesity (DIO) by preventing weight gain, improving serum blood parameters, enhancing energy expenditure, stimulating white fat browning, and reversing hepatic steatosis. Further investigations demonstrated that BP administration upregulated the mRNA expression of beige (CD137, TMEM26) and brown fat selected genes (UCP1, PRDM16, PGC-1α, PPARγ) in white adipose tissues. In vitro studies, BP treatment increased multilocular lipid droplet levels, induced β-adrenergic receptor (cAMP/PKA) and AMP-activated protein kinase (AMPK) signaling (AMPK/acetyl-CoA carboxylase/SIRT1), and increased oxygen consumption in murine differentiated beige adipocytes, and the effects of BP were blocked by an AMPK inhibitor. BP promoted the interaction of AMPK with PGC-1α in beige adipocytes. Our findings provide novel insights into the application of BP in regulating energy metabolism and suggest its utility for clinical use in the treatment of obesity and related diseases.
棕色脂肪组织（BAT）中的产热（非运动活动）因其比白色脂肪组织（WAT）更多的线粒体而促进能量消耗。BAT 中产热的主要功能可以通过将卡路里散发为热量来对抗肥胖。丁烯基苯酞（BP）是当归的一种天然衍生物，当归是一种中国草药，已经使用了数千年。在本报告中，我们证明 BP 通过防止体重增加、改善血清血液参数、增强能量消耗、刺激白色脂肪褐变和逆转肝脂肪变性，改善高脂肪饮食诱导肥胖（DIO）小鼠的代谢特征。进一步的研究表明，BP 给药上调了白色脂肪组织中米色（CD137、TMEM26）和棕色脂肪选择基因（UCP1、PRDM16、PGC-1α、PPARγ）的 mRNA 表达。体外研究表明，BP 处理增加了多泡脂质滴水平，诱导β-肾上腺素能受体（cAMP/PKA）和 AMP 激活的蛋白激酶（AMPK）信号（AMPK/乙酰辅酶 A 羧化酶/SIRT1），并增加了鼠分化的米色脂肪细胞中的耗氧量，而 AMPK 抑制剂阻断了 BP 的作用。BP 促进了 AMPK 与米色脂肪细胞中 PGC-1α 的相互作用。我们的发现为 BP 调节能量代谢的应用提供了新的见解，并表明其在肥胖症和相关疾病的临床治疗中的应用潜力。
