Dietary abscisic acid ameliorates glucose tolerance and obesity-related inflammation in db/db mice fed high-fat diets

Background & Aims Despite their efficacy in improving insulin sensitivity, thiazolidinediones (TZDs) are associated with a number of side effects (i.e. weight gain, hepatotoxicity, congestive heart failure) that have limited their use by millions of diabetic patients. We have investigated whether abscisic acid (ABA), a naturally occurring phytochemical with structural similarities to TZDs, could be used as an alternative to TZDs to improve glucose homeostasis. Methods We first examined whether ABA, similar to TZDs, activates PPARγ in vitro. We next determined the lowest effective dose of dietary ABA (100 mg/kg) and assessed its effect on glucose tolerance, obesity-related inflammation, and mRNA expression of PPARγ and its responsive genes in white adipose tissue (WAT) of db/db mice fed high-fat diets. Results We found that ABA induced transactivation of PPARγ in 3T3-L1 pre-adipocytes in vitro. Dietary ABA-supplementation for 36 days decreased fasting blood glucose concentrations, ameliorated glucose tolerance, and increased mRNA expression of PPARγ and its responsive genes (i.e., adiponectin, aP2, and CD36) in WAT. We also found that adipocyte hypertrophy, tumor necrosis factor-α (TNF-α) expression, and macrophage infiltration in WAT were significantly attenuated in ABA-fed mice. Conclusions These findings suggest that ABA could be used as a nutritional intervention against type II diabetes and obesity-related inflammation.