Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
Laboratory of Animal Fat Deposition and Muscle Development, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
J Biol Chem. 2024 Sep;300(9):107721. doi: 10.1016/j.jbc.2024.107721. Epub 2024 Aug 29.
Obesity has emerged as a major health risk on a global scale. Hinokiflavone (HF), a natural small molecule, extracted from plants like cypress, exhibits diverse chemical structures and low synthesis costs. Using high-fat diet-induced obese mice models, we found that HF suppresses obesity by inducing apoptosis in adipose tissue. Adipocyte apoptosis helps maintain tissue health by removing aging, damaged, or excess cells in adipose tissue, which is crucial in preventing obesity and metabolic diseases. We found that HF can specifically bind to insulin-like growth factor 2 mRNA binding protein 2 to promote the stability of N6-methyladenosine-modified Bim, inducing mitochondrial outer membrane permeabilization. Mitochondrial outer membrane permeabilization leads to Caspase9/3-mediated adipocyte mitochondrial apoptosis, alleviating obesity induced by a high-fat diet. The proapoptotic effect of HF offers a controlled means for weight loss. This study reveals the potential of small molecule HF in developing new therapeutic approaches in drug development and biomedical research.
肥胖已成为全球范围内的主要健康风险。松脂素（HF）是一种从柏木等植物中提取的天然小分子，具有多样化的化学结构和低廉的合成成本。我们利用高脂肪饮食诱导的肥胖小鼠模型发现，HF 通过诱导脂肪组织细胞凋亡来抑制肥胖。脂肪细胞凋亡有助于通过去除脂肪组织中衰老、受损或多余的细胞来维持组织健康，这对于预防肥胖和代谢性疾病至关重要。我们发现，HF 可以特异性结合胰岛素样生长因子 2 mRNA 结合蛋白 2（IGF2BP2），促进 N6-甲基腺苷（m6A）修饰的 Bim 的稳定性，诱导线粒体膜通透性转换。线粒体膜通透性转换导致 Caspase9/3 介导的脂肪细胞线粒体凋亡，从而缓解高脂肪饮食诱导的肥胖。HF 的促凋亡作用为减肥提供了一种可控手段。本研究揭示了小分子 HF 在药物开发和生物医学研究中开发新治疗方法的潜力。
