Rahman Md Shamim, Kim Yong-Sik
Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University, Cheonan, Chung-nam, 31151, Republic of Korea; Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan, Chung-nam, 31151, Republic of Korea.
Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University, Cheonan, Chung-nam, 31151, Republic of Korea; Department of Microbiology, College of Medicine, Soonchunhyang University, Cheonan, Chung-nam, 31151, Republic of Korea.
Food Chem Toxicol. 2020 Jul;141:111415. doi: 10.1016/j.fct.2020.111415. Epub 2020 May 14.
Mangiferin (MF) from Mangifera indica has been serendipitously found to ameliorate obesity and is used as an antioxidant, anti-inflammatory, antimicrobial, and anticancer agent. Nonetheless, the mechanism of MF-induced brown-adipose-tissue activation has not been studied. Therefore, we investigated the effect of MF on thermogenic features during brown-adipocyte differentiation. Treatment with MF improved the expression of a brown-fat signature and of mitochondrial-mass-related genes, thus resulting in UCP1 induction. MF also raised the expression of other thermogenic regulators, including peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), PR domain-containing protein 16 (PRDM16), and peroxisome proliferator-activated receptors alpha and gamma (PPAR-α and -γ). MF promoted mitochondrial biogenesis, judging by increased expression of cell death-inducing DNA fragmentation factor α-like effector A (CIDEA), mitochondrial transcription factor A (TFAM), iodothyronine deiodinase 2 (DIO2), cytochrome c oxidase subunit 7A (COX7A), cyclooxygenase 2 (COX2), sirtuin 1 (SIRT1), and nuclear respiratory factor 1 (NRF1). MF treatment increased the mitochondrial DNA amount and improved mitochondrial respiratory function by increasing the oxygen consumption rate during brown-adipocyte differentiation. A gene knockdown assay involving small interfering RNA and competitive inhibition with dorsomorphin revealed that MF may promote thermogenesis in brown preadipocytes via activation of AMPK signaling. Collectively, our findings suggest that MF may be a novel pharmaceutical agent that can ameliorate obesity via activation of brown adipose tissue.
人们意外发现，芒果中的芒果苷（MF）可改善肥胖状况，并且它还具有抗氧化、抗炎、抗菌和抗癌作用。然而，MF诱导棕色脂肪组织激活的机制尚未得到研究。因此，我们研究了MF在棕色脂肪细胞分化过程中对产热特性的影响。用MF处理可改善棕色脂肪标志性基因以及与线粒体质量相关基因的表达，从而导致解偶联蛋白1（UCP1）的诱导。MF还提高了其他产热调节因子的表达，包括过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1α）、含PR结构域蛋白16（PRDM16）以及过氧化物酶体增殖物激活受体α和γ（PPAR-α和 -γ）。从细胞死亡诱导DNA片段化因子α样效应因子A（CIDEA）、线粒体转录因子A（TFAM）、碘甲腺原氨酸脱碘酶2（DIO2）、细胞色素c氧化酶亚基7A（COX7A）、环氧化酶2（COX2）、沉默调节蛋白1（SIRT1）和核呼吸因子1（NRF1）表达的增加可以判断，MF促进了线粒体生物合成。在棕色脂肪细胞分化过程中，MF处理增加了线粒体DNA的量，并通过提高耗氧率改善了线粒体呼吸功能。一项涉及小干扰RNA的基因敲低试验以及与 dorsomorphin的竞争性抑制试验表明，MF可能通过激活AMPK信号通路促进棕色前脂肪细胞的产热。总的来说，我们的研究结果表明，MF可能是一种新型药剂，可通过激活棕色脂肪组织来改善肥胖状况。
