Funakoshi-Tago Megumi, Hattori Takahiro, Ueda Fumihito, Tago Kenji, Ohe Tomoyuki, Mashino Tadahiko, Tamura Hiroomi
Department of Hygienic Chemistry, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan.
Division of Structural Biochemistry, Department of Biochemistry, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi-ken 329-0498, Japan.
Biochem Biophys Rep. 2016 Jan 8;5:259-265. doi: 10.1016/j.bbrep.2016.01.001. eCollection 2016 Mar.
Obesity and its associated metabolic diseases represent some of the most rapidly expanding health issues worldwide, and, thus, the development of a novel chemical compound to suppress adipogenesis is strongly expected. We herein investigated the effects of water-soluble fullerene derivatives: a bis-malonic acid derivative and three types of proline-type fullerene derivatives, on adipogenesis using NIH-3T3 cells overexpressing PPARγ. One of the proline-type fullerene derivatives (P3) harboring three carboxy groups significantly inhibited lipid accumulation and the expression of adipocyte-specific genes, such as aP2, induced by the PPARγ agonist rosiglitazone. On the other hand, the bis-malonic acid derivative (M) and the 2 other proline-type fullerene derivatives (P1, P2), which have two carboxy groups, had no effect on PPARγ-mediated lipid accumulation or the expression of aP2. P3 fullerene also inhibited lipid accumulation induced by the combined stimulation with 3-isobutyl-1-methylxanthine (IBMX), dexamethasone, and insulin in 3T3-L1 preadipocytes. During the differentiation of 3T3-L1 cells into adipocytes, P3 fullerene did not affect the expression of C/EBPδ, C/EBPβ, or PPARγ, but markedly inhibited that of aP2 mRNA. These results suggest that P3 fullerene exhibits anti-obesity activity by preventing the activation of PPARγ.
肥胖及其相关的代谢性疾病是全球范围内迅速蔓延的一些最严重的健康问题，因此，人们强烈期待开发出一种新型化合物来抑制脂肪生成。我们在此研究了水溶性富勒烯衍生物：一种双丙二酸衍生物和三种脯氨酸型富勒烯衍生物，对过表达PPARγ的NIH-3T3细胞脂肪生成的影响。其中一种带有三个羧基的脯氨酸型富勒烯衍生物（P3）显著抑制了由PPARγ激动剂罗格列酮诱导的脂质积累以及脂肪细胞特异性基因（如aP2）的表达。另一方面，具有两个羧基的双丙二酸衍生物（M）和另外两种脯氨酸型富勒烯衍生物（P1、P2）对PPARγ介导的脂质积累或aP2的表达没有影响。P3富勒烯还抑制了3T3-L1前脂肪细胞中由3-异丁基-1-甲基黄嘌呤（IBMX）、地塞米松和胰岛素联合刺激诱导的脂质积累。在3T3-L1细胞向脂肪细胞分化的过程中，P3富勒烯不影响C/EBPδ、C/EBPβ或PPARγ的表达，但显著抑制aP2 mRNA的表达。这些结果表明，P3富勒烯通过阻止PPARγ的激活表现出抗肥胖活性。
