Research and Education Faculty, Multidisciplinary Science Cluster, Interdisciplinary Science Unit, Kochi University, Kochi, 783-8505, Japan; Department of Marine Resource Science, Faculty of Agriculture and Marine Science, Kochi University, Kochi, 783-8502, Japan.
Department of Marine Resource Science, Faculty of Agriculture and Marine Science, Kochi University, Kochi, 783-8502, Japan.
Biochem Biophys Res Commun. 2023 Oct 20;678:200-206. doi: 10.1016/j.bbrc.2023.08.054. Epub 2023 Aug 24.
Obesity increases the risk of various diseases, and many studies have examined prevention and treatment strategies. Browning of white adipocytes promotes triglyceride (TG) metabolism and is the new focus for treating obesity. This study investigated the role of malonate-a modulator of mitochondrial function-in adipocyte browning, and its potential as a therapeutic agent in obesity. Our findings revealed that malonate increased oxygen consumption without inhibiting ATP synthesis. Malonate induced expression of PRDM16-an important transcription factor for browning-and uncoupling protein 1 (beige adipocyte marker), suggesting that malonate induces browning in white adipocytes. In an obesity mouse model induced by a high-fat diet, malonate significantly reduced body weight and white adipose tissue weight, as well as improved insulin resistance. Importantly, malonate stimulated browning in white adipose tissue and maintained the mass of brown adipose tissue in the high-fat diet-induced obesity mouse model. We propose that manipulation of mitochondrial function by malonate is a promising therapeutic approach for obesity.
肥胖会增加罹患各种疾病的风险，许多研究都在探讨预防和治疗策略。白色脂肪细胞的棕色化促进甘油三酯（TG）代谢，成为治疗肥胖的新焦点。本研究探讨了丙二酸盐（一种线粒体功能调节剂）在脂肪细胞棕色化中的作用及其作为肥胖治疗药物的潜力。我们的研究结果表明，丙二酸盐在不抑制 ATP 合成的情况下增加耗氧量。丙二酸盐诱导 PRDM16（棕色化的重要转录因子）和解偶联蛋白 1（米色脂肪细胞标志物）的表达，表明丙二酸盐可诱导白色脂肪细胞的棕色化。在高脂肪饮食诱导的肥胖小鼠模型中，丙二酸盐可显著降低体重和白色脂肪组织重量，改善胰岛素抵抗。重要的是，丙二酸盐可刺激白色脂肪组织的棕色化，并维持高脂肪饮食诱导的肥胖小鼠模型中棕色脂肪组织的质量。我们提出，丙二酸盐对线粒体功能的操纵可能是肥胖症的一种有前途的治疗方法。
