Department of Nutritional Science, Chung Shan Medical University, No. 110 Sec 1 Jianguo N. Rd, Taichung, Taiwan, ROC.
Graduate Institute of Veterinary Pathology, College of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
Eur J Nutr. 2021 Jun;60(4):1781-1793. doi: 10.1007/s00394-020-02371-5. Epub 2020 Aug 28.
The major aim of the present study was to determine the effects of quercetin, a well-known flavonoid, on attenuating cisplatin (CDDP)-induced fat loss and the possible mechanisms.
Tumor-bearing nude mice and tumor-free BALB/c mice were administrated with CDDP alone or in combination with quercetin by a diet containing 0.1% or 1% quercetin (LQ or HQ) or by intraperitoneal injection (IQ) to determine the effects of quercetin on the anticancer effect of CDDP or CDDP-induced fat loss. The effects of quercetin on fat accumulation in CDDP-exposed 3T3-L1 cells were also determined.
We first showed that HQ and IQ significantly enhanced the anticancer effect of CDDP by upregulating p53- and p21-associated pathways, while tended to attenuate CDDP-induced fat loss in tumor-bearing nude mice. The study in 3T3-L1 cells showed that CDDP decreased the fat accumulation accompanied by strong upregulation of the expression of six genes which are associated with fat metabolism, while quercetin completely suppressed such an effect. The tumor-free BALB/c mice study consistently showed a protective effect of HQ on CDDP-induced body weight and epididymal fat loss. HQ also increased the fat levels in liver and muscle tissues. In epididymal fat tissues, HQ consistently attenuated CDDP-induced changes in fat metabolism-associated gene expression. However, CDDP alone or in combination with HQ did not affect the food intake.
This study demonstrates that quercetin possesses the potential to suppress CDDP-induced fat loss may partly through the regulation of the fat metabolism-associated gene expression.
本研究的主要目的是确定一种众所周知的黄酮类化合物槲皮素对减轻顺铂（CDDP）诱导的脂肪损失的影响及其可能的机制。
用含有 0.1%或 1%槲皮素（LQ 或 HQ）的饮食或腹腔注射（IQ）单独或联合给予荷瘤裸鼠和无瘤 BALB/c 小鼠 CDDP，以确定槲皮素对 CDDP 的抗癌作用或 CDDP 诱导的脂肪损失的影响。还确定了槲皮素对暴露于 CDDP 的 3T3-L1 细胞中脂肪积累的影响。
我们首先表明，HQ 和 IQ 通过上调 p53 和 p21 相关途径显著增强了 CDDP 的抗癌作用，同时倾向于减轻荷瘤裸鼠中 CDDP 诱导的脂肪损失。在 3T3-L1 细胞中的研究表明，CDDP 减少了脂肪积累，同时强烈上调了六个与脂肪代谢相关的基因的表达，而槲皮素完全抑制了这种作用。无瘤 BALB/c 小鼠的研究一致表明 HQ 对 CDDP 诱导的体重和附睾脂肪损失具有保护作用。HQ 还增加了肝和肌肉组织中的脂肪水平。在附睾脂肪组织中，HQ 一致减轻了 CDDP 诱导的与脂肪代谢相关的基因表达变化。然而，CDDP 单独或与 HQ 联合使用并不影响食物摄入。
本研究表明，槲皮素有抑制 CDDP 诱导的脂肪损失的潜力，部分可能是通过调节与脂肪代谢相关的基因表达。
