Aranaz Paula, Navarro-Herrera David, Zabala María, Romo-Hualde Ana, López-Yoldi Miguel, Vizmanos José Luis, Milagro Fermín I, González-Navarro Carlos J
Center for Nutrition Research, School of Pharmacy and Nutrition, University of Navarra, 31008 Pamplona, Spain.
Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain.
Pharmaceuticals (Basel). 2020 Oct 30;13(11):355. doi: 10.3390/ph13110355.
Supplementation with bioactive compounds capable of regulating energy homeostasis is a promising strategy to manage obesity. Here, we have screened the ability of different phenolic compounds (myricetin, kaempferol, naringin, hesperidin, apigenin, luteolin, resveratrol, curcumin, and epicatechin) and phenolic acids (-coumaric, ellagic, ferulic, gallic, and vanillic acids) regulating fat accumulation. Resveratrol exhibited the strongest lipid-reducing activity, which was accompanied by the improvement of lifespan, oxidative stress, and aging, without affecting worm development. Whole-genome expression microarrays demonstrated that resveratrol affected fat mobilization, fatty acid metabolism, and unfolded protein response of the endoplasmic reticulum (UPR), mimicking the response to calorie restriction. Apigenin induced the oxidative stress response and lipid mobilization, while vanillic acid affected the unfolded-protein response in ER. In summary, our data demonstrates that phenolic compounds exert a lipid-reducing activity in through different biological processes and signaling pathways, including those related with lipid mobilization and fatty acid metabolism, oxidative stress, aging, and UPR-ER response. These findings open the door to the possibility of combining them in order to achieve complementary activity against obesity-related disorders.
补充能够调节能量平衡的生物活性化合物是控制肥胖的一种有前景的策略。在此,我们筛选了不同酚类化合物(杨梅素、山奈酚、柚皮苷、橙皮苷、芹菜素、木犀草素、白藜芦醇、姜黄素和表儿茶素)以及酚酸(对香豆酸、鞣花酸、阿魏酸、没食子酸和香草酸)调节脂肪积累的能力。白藜芦醇表现出最强的降脂活性,同时伴随着寿命延长、氧化应激改善和衰老延缓,且不影响线虫发育。全基因组表达微阵列表明,白藜芦醇影响脂肪动员、脂肪酸代谢以及内质网未折叠蛋白反应(UPR),模拟了对热量限制的反应。芹菜素诱导氧化应激反应和脂质动员,而香草酸影响内质网中的未折叠蛋白反应。总之,我们的数据表明酚类化合物通过不同的生物学过程和信号通路发挥降脂活性,包括那些与脂质动员、脂肪酸代谢、氧化应激、衰老和内质网未折叠蛋白反应相关的过程和通路。这些发现为将它们组合起来以实现针对肥胖相关疾病的互补活性提供了可能性。