Nobushi Yasuhito, Wada Taira, Miura Motofumi, Onoda Rikuto, Ishiwata Ryuta, Oikawa Naoki, Shigematsu Karin, Nakakita Toshinori, Toriyama Masaharu, Shimba Shigeki, Kishikawa Yukinaga
Laboratory of Clinical Pharmacy, School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi 274-8555, Chiba, Japan.
Laboratory of Health Science, School of Pharmacy, Nihon University, 7-7-1, Narashinodai, Funabashi 274-8555, Chiba, Japan.
Life (Basel). 2024 Nov 7;14(11):1446. doi: 10.3390/life14111446.
Flavanones, a class of flavonoids, are abundant in fruits, vegetables, and herbs. They are known to have several biological activities, such as anti-inflammatory and anti-cancer activities, but their effects on obesity remain unclear. Obesity is closely associated with adipocyte differentiation and lipid accumulation in adipose tissue. Therefore, in this study, we examined the effects of flavanone derivatives on adipocyte differentiation and lipid accumulation by using 3T3-L1 cells. Among the 15 flavanone derivatives studied, 4'-phenylflavanone (4PF), with a biphenyl structure, significantly inhibited adipocyte differentiation-related lipid accumulation in 3T3-L1 cells; this inhibition of lipid accumulation was dose-dependent. Gene expression analysis showed that 4PF suppressed the expression of adipogenic marker genes. Although the induction of (), a master regulator of adipocyte differentiation, and its target genes during adipocyte differentiation was attenuated in 4PF-treated cells, 4PF did not directly regulate gene expression and its activation. In contrast, 4PF suppressed mitotic clonal expansion (MCE), which is associated with changes in the expression of proliferation-related genes at the early stages of adipocyte differentiation. Taken together, these results suggest that 4PF inhibits lipid accumulation because it suppresses MCE during adipocyte differentiation. Thus, our findings may help in the development of anti-obesity drugs.
黄烷酮是一类黄酮类化合物,在水果、蔬菜和草药中含量丰富。已知它们具有多种生物活性,如抗炎和抗癌活性,但其对肥胖的影响尚不清楚。肥胖与脂肪组织中的脂肪细胞分化和脂质积累密切相关。因此,在本研究中,我们使用3T3-L1细胞研究了黄烷酮衍生物对脂肪细胞分化和脂质积累的影响。在所研究的15种黄烷酮衍生物中,具有联苯结构的4'-苯基黄烷酮(4PF)显著抑制了3T3-L1细胞中与脂肪细胞分化相关的脂质积累;这种脂质积累的抑制呈剂量依赖性。基因表达分析表明,4PF抑制了脂肪生成标记基因的表达。尽管在4PF处理的细胞中,脂肪细胞分化的主要调节因子()及其靶基因在脂肪细胞分化过程中的诱导作用减弱,但4PF并未直接调节基因表达及其激活。相反,4PF抑制了有丝分裂克隆扩增(MCE),这与脂肪细胞分化早期增殖相关基因表达的变化有关。综上所述,这些结果表明4PF抑制脂质积累是因为它在脂肪细胞分化过程中抑制了MCE。因此,我们的发现可能有助于抗肥胖药物的开发。