Talks
Presentation Type
Oral Presentation
Discipline Track
Biomedical Science
Abstract Type
Research/Clinical
Abstract
Background: Type 2 diabetes (T2D) is characterized by insulin resistance, an impaired response to insulin by cells. Although several medications target insulin sensitivity, they fail to prevent progression to T2D in most high-risk individuals. Oleanolic acid (OA) is a pentacyclic triterpenoid found in plants with unique cardioprotective and anti-diabetic properties. OA can serve as a scaffold to produce synthetic molecules, known as synthetic oleanane triterpenoids (SOs), with enhanced biological activity. Our published findings show that the SO CDDO-EA (2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-ethyl amide) facilitates translocation of the glucose transporter protein, GLUT4, as a new mechanism of CDDO-EA in regulating glucose metabolism. Thus, we hypothesize that CDDO-EA prevents glucose intolerance to protect from the development of T2D.
Methods: CDDO-EA was synthesized in powder form from OA via CDDO-methyl ester. The final product, CDDO-EA, was analyzed by high performance liquid chromatography (HPLC) and atmospheric pressure ionization/mass spectrometry (APCI-MS) to determine the purity and confirm the exact molecular formula. C57BL/6J mice (6 – 8 weeks old, male) were fed a low- fat diet (LFD, 10% of total calories from fat) or a high-fat diet (HFD, 60% of total calories from fat) with or without CDDO-EA (diet containing 0.04% CDDO-EA) for six weeks. Mice were unrestrained and awake throughout the collection of blood samples, oral glucose tolerance tests (OGTTs), and measurements of body weight. Blood samples were collected via tail snip before the start of experimental feeding and then every two weeks. Glucose levels were measured using a glucometer, and insulin concentrations were measured using an ELISA. Mice were weighed once a week. OGTTs were performed after the six-week experimental feeding.
Results: HPLC showed high purity (>99%) and APCI-MS showed the correct mass and fragmentation pattern of the synthesized CDDO-EA. Mice fed a HFD weighed significantly more than the LFD fed animals by week two, and this was consistent throughout the six-week study. The incorporation of CDDO-EA in the HFD prevented excess weight gain in mice fed a HFD. Further, CDDO-EA decreased energy intake in mice fed a HFD. Serum glucose levels were significantly increased in mice fed only a HFD at 2 weeks and remained significantly increased throughout the rest of the feeding. Serum glucose levels in mice fed a HFD with CDDO-EA did not increase throughout the six-week feeding. In addition, serum insulin levels were significantly higher at 2 weeks and remained significantly higher in mice fed only a HFD compared to mice fed a HFD with CDDO-EA. OGTTs showed that CDDO-EA prevented increased serum glucose and insulin concentrations in mice fed a HFD. The HFD + CDDO-EA group’s glucose levels overlap with the HFD up to the 45 min. timepoint and then significantly decrease to glucose levels before experimental feeding. The HFD+CDDO-EA group insulin levels did not increase significantly and did overlap with the insulin levels before experimental feeding.
Conclusions: CDDO-EA prevents obesity due to decreased food intake and protects from hyperglycemia, hyperinsulinemia, and glucose intolerance. Our findings show for the first time that CDDO-EA has the potential to prevent insulin resistance and T2D.
Recommended Citation
Cantu, A.; Cantu, Denae; Rasa, Cordelia; Mito, Shizue; Lopez-Alvarenga, Juan C.; and Reyna, Sara M., "Triterpenoid CDDO-EA Protects from Obesity and Insulin Resistance in an Animal Model of Type 2 Diabetes" (2024). Research Symposium. 20.
https://scholarworks.utrgv.edu/somrs/2023/talks/20
Included in
Triterpenoid CDDO-EA Protects from Obesity and Insulin Resistance in an Animal Model of Type 2 Diabetes
Background: Type 2 diabetes (T2D) is characterized by insulin resistance, an impaired response to insulin by cells. Although several medications target insulin sensitivity, they fail to prevent progression to T2D in most high-risk individuals. Oleanolic acid (OA) is a pentacyclic triterpenoid found in plants with unique cardioprotective and anti-diabetic properties. OA can serve as a scaffold to produce synthetic molecules, known as synthetic oleanane triterpenoids (SOs), with enhanced biological activity. Our published findings show that the SO CDDO-EA (2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid-ethyl amide) facilitates translocation of the glucose transporter protein, GLUT4, as a new mechanism of CDDO-EA in regulating glucose metabolism. Thus, we hypothesize that CDDO-EA prevents glucose intolerance to protect from the development of T2D.
Methods: CDDO-EA was synthesized in powder form from OA via CDDO-methyl ester. The final product, CDDO-EA, was analyzed by high performance liquid chromatography (HPLC) and atmospheric pressure ionization/mass spectrometry (APCI-MS) to determine the purity and confirm the exact molecular formula. C57BL/6J mice (6 – 8 weeks old, male) were fed a low- fat diet (LFD, 10% of total calories from fat) or a high-fat diet (HFD, 60% of total calories from fat) with or without CDDO-EA (diet containing 0.04% CDDO-EA) for six weeks. Mice were unrestrained and awake throughout the collection of blood samples, oral glucose tolerance tests (OGTTs), and measurements of body weight. Blood samples were collected via tail snip before the start of experimental feeding and then every two weeks. Glucose levels were measured using a glucometer, and insulin concentrations were measured using an ELISA. Mice were weighed once a week. OGTTs were performed after the six-week experimental feeding.
Results: HPLC showed high purity (>99%) and APCI-MS showed the correct mass and fragmentation pattern of the synthesized CDDO-EA. Mice fed a HFD weighed significantly more than the LFD fed animals by week two, and this was consistent throughout the six-week study. The incorporation of CDDO-EA in the HFD prevented excess weight gain in mice fed a HFD. Further, CDDO-EA decreased energy intake in mice fed a HFD. Serum glucose levels were significantly increased in mice fed only a HFD at 2 weeks and remained significantly increased throughout the rest of the feeding. Serum glucose levels in mice fed a HFD with CDDO-EA did not increase throughout the six-week feeding. In addition, serum insulin levels were significantly higher at 2 weeks and remained significantly higher in mice fed only a HFD compared to mice fed a HFD with CDDO-EA. OGTTs showed that CDDO-EA prevented increased serum glucose and insulin concentrations in mice fed a HFD. The HFD + CDDO-EA group’s glucose levels overlap with the HFD up to the 45 min. timepoint and then significantly decrease to glucose levels before experimental feeding. The HFD+CDDO-EA group insulin levels did not increase significantly and did overlap with the insulin levels before experimental feeding.
Conclusions: CDDO-EA prevents obesity due to decreased food intake and protects from hyperglycemia, hyperinsulinemia, and glucose intolerance. Our findings show for the first time that CDDO-EA has the potential to prevent insulin resistance and T2D.