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Oleanolic acid induces a dual agonist action on PPARγ/α and GLUT4 translocation: A pentacyclic triterpene for dyslipidemia and type 2 diabetes.

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Type 2 diabetes (T2D) is a metabolic disease characterized by defects in glycemia regulation. This disease is associated with alterations in insulin action and lipid metabolism, generating hyperglycemia and dyslipidemias.… Click to show full abstract

Type 2 diabetes (T2D) is a metabolic disease characterized by defects in glycemia regulation. This disease is associated with alterations in insulin action and lipid metabolism, generating hyperglycemia and dyslipidemias. Currently, it is necessary to develop new or known drugs that promote the sensitization of insulin action. Thus, activation of peroxisome proliferator-activated receptors (PPARs) is probably the key to doing this. PPARs participate in maintaining an energetic balance between storage and the expenditure of energy. The activation of PPARγ produces the storage of energy, mainly as glycogen and fat. Meanwhile, PPARα activation promotes lipid degradation. As previously described, Oleanolic acid (OA), a pentacyclic triterpenoid of numerous edible and medicinal plants, decreases hyperglycemia and lipid accumulation. However, the effects on PPAR and their regulated genes are unknown. Our aim was to determine the effects of OA on PPAR γ/α expression and their regulated genes (adiponectin, type 4 glucose transporter, fatty acid transport protein, and long-chain acyl-CoA synthetase) in C2C12 myoblasts by RT-PCR, Western blot, GLUT4 translocation, and lipid storage in 3T3-L1 adypocites. In C2C12 myoblasts, OA increased the expression of mRNA in both PPARγ/α and their regulated genes; also, PPARγ, GLUT4, and FATP1 protein expression increased, as well as GLUT4 translocation. In 3T3-L1, OA increased the expression of mRNA in both PPARγ/α and maintained lipid storage unchanged. In conclusion, OA exhibited a dual action on PPARγ/α, which might explain in part its antihyperglycemic effect. This compound represents an alternative for designing novel therapeutic strategies in the control of T2D.

Keywords: ppar; glut4 translocation; type diabetes; oleanolic acid; action

Journal Title: European journal of pharmacology
Year Published: 2020

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