Cantu Austin E, Rasa Cordelia, Mito Shizue, Cantu Denae, Lopez-Alvarenga Juan Carlos, Rivera-Lopez Leslie L, Rios Israel, Abrego-Gonzalez Ashley, Reyna Sara M
Baylor College of Medicine, Houston, TX 76798, USA.
Department of Laboratory Animal Resources, The University of Texas Rio Grande Valley, Edinburg, TX 78539, USA.
Int J Mol Sci. 2025 Jun 7;26(12):5485. doi: 10.3390/ijms26125485.
Obesity is a significant factor in the development of type 2 diabetes (T2D). Treatment of obesity is pivotal in the prevention and management of T2D, and the development of new pharmacological therapies are studied for improving insulin resistance and glucose intolerance. Oleanolic acid-derived triterpenoids, 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acids (CDDOs), are studied to elucidate the mechanisms by which they protect against obesity. However, fundamental knowledge gaps remain regarding the physiological and molecular mechanisms by which CDDOs protect against obesity. Our recently published studies showed that CDDO-ethyl amide (CDDO-EA) prevents skeletal muscle inflammation by inhibiting activation of nuclear factor-kappa B (NF-κB) signaling. Moreover, CDDO-EA induced translocation of glucose transporter 4, GLUT4, in skeletal muscle cells. We hypothesized that CDDO-EA protects from obesity-induced hyperglycemia in mice fed a high-fat diet (HFD). Our results show that CDDO-EA protects from HFD-induced obesity but has no effect on body weight in mice fed a low-fat diet (LFD). Our data show that CDDO-EA inhibition of weight gain is associated with reduced caloric intake and glucose and insulin levels in mice fed an HFD. This highlights the potential of CDDO-EA as a therapeutic agent for obesity treatment and the protection against the development of T2D.
肥胖是2型糖尿病（T2D）发病的一个重要因素。肥胖的治疗对于T2D的预防和管理至关重要，人们正在研究开发新的药物疗法以改善胰岛素抵抗和葡萄糖耐受不良。对源自齐墩果酸的三萜类化合物2-氰基-3,12-二氧代齐墩果-1,9-二烯-28-酸（CDDOs）进行了研究，以阐明它们预防肥胖的机制。然而，关于CDDOs预防肥胖的生理和分子机制仍存在一些基本知识空白。我们最近发表的研究表明，CDDO-乙酰胺（CDDO-EA）通过抑制核因子-κB（NF-κB）信号通路的激活来预防骨骼肌炎症。此外，CDDO-EA可诱导骨骼肌细胞中葡萄糖转运蛋白4（GLUT4）的转位。我们假设CDDO-EA可保护高脂饮食（HFD）喂养的小鼠免受肥胖诱导的高血糖影响。我们的结果表明，CDDO-EA可保护小鼠免受HFD诱导的肥胖，但对低脂饮食（LFD）喂养的小鼠体重没有影响。我们的数据表明，CDDO-EA对体重增加的抑制作用与HFD喂养小鼠的热量摄入减少以及血糖和胰岛素水平降低有关。这突出了CDDO-EA作为肥胖治疗和预防T2D发生的治疗剂的潜力。
