Rendine Marco, Venturi Samuele, Marino Mirko, Gardana Claudio, Møller Peter, Martini Daniela, Riso Patrizia, Del Bo Cristian
Division of Human Nutrition, Department of Food, Environmental and Nutritional Sciences (DeFENS), Università degli Studi di Milano, Milan, Italy.
Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
Mol Nutr Food Res. 2025 Apr 21:e70070. doi: 10.1002/mnfr.70070.
The aim of the study was to assess the effects of quercetin metabolites (QMs) on lipid accumulation in adipocytes under high-glucose and physiological-glucose concentrations and to elucidate the mechanisms involved. 3T3-L1 mature adipocytes were exposed to a physiological glucose concentration, as a model of caloric restriction (CR), or high glucose (control), with and without QMs (quercetin-3-glucuronide [Q3G] and isorhamnetin [ISOR]). Cells were treated with Q3G (0.3 and 0.6 µmol/L) and ISOR (0.2 and 0.4 µmol/L) for 48 h. Lipid accumulation (Oil Red O staining) and Δ glucose level (HPLC) were assessed. Under high glucose, Q3G and ISOR reduced lipid accumulation (-10.8% and -10.4%; p < 0.01) and Δ glucose level (-13.6% and -14.2%; p < 0.05). Under CR, QMs increased Δ glucose level (+21.6% for Q3G and +21% for ISOR; p < 0.05). ISOR increased pAMPK levels under high glucose (+1.4-fold; p < 0.05). Under CR, Q3G and ISOR increased pAMPK (+1.4- and +1.5-fold; p < 0.05), while ISOR upregulated SIRT1 and PGC-1α (+2.3- and +1.5-fold; p < 0.05). Findings support, for the first time, the potential contribution of QMs, especially ISOR, in the regulation of lipid metabolism in vitro, possibly via AMPK activation. Further studies, including in vivo, are encouraged to strengthen evidence of the mechanisms observed.
本研究的目的是评估槲皮素代谢产物（QMs）在高糖和生理葡萄糖浓度下对脂肪细胞脂质积累的影响，并阐明其中涉及的机制。将3T3-L1成熟脂肪细胞暴露于生理葡萄糖浓度（作为热量限制[CR]模型）或高糖（对照）环境中，同时添加或不添加QMs（槲皮素-3-葡萄糖醛酸苷[Q3G]和异鼠李素[ISOR]）。用Q3G（0.3和0.6 μmol/L）和ISOR（0.２和0.4 μmol/L）处理细胞48小时。评估脂质积累（油红O染色）和葡萄糖水平变化（高效液相色谱法）。在高糖条件下，Q3G和ISOR可减少脂质积累（分别为-10.8%和-10.4%；p<0.01）以及葡萄糖水平变化（分别为-13.6%和-14.2%；p<0.05）。在热量限制条件下，QMs可提高葡萄糖水平变化（Q3G为+21.6%，ISOR为+21%；p<0.05）。在高糖条件下，ISOR可提高磷酸化腺苷酸活化蛋白激酶（pAMPK）水平（增加1.4倍；p<0.05）。在热量限制条件下，Q3G和ISOR可提高pAMPK水平（分别增加1.4倍和1.5倍；p<0.05），而ISOR可上调沉默信息调节因子1（SIRT1）和过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC-1α）水平（分别增加2.3倍和1.5倍；p<0.05）。这些发现首次证实了QMs，尤其是ISOR，可能通过激活AMPK在体外调节脂质代谢中的潜在作用。鼓励开展进一步研究，包括体内研究，以加强对所观察到机制的证据支持。
