Triterpenoid CDDO-EA Protects from Hyperglycemia, Hyperinsulinemia, and Obesity by Decreasing Energy Intake

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.