Dietary abscisic acid ameliorates glucose tolerance and obesity-related inflammation in db/db mice fed high-fat diets.
OBJECTIVE
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 PPARgamma 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 PPARgamma 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 PPARgamma 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 PPARgamma and its responsive genes (i.e., adiponectin, aP2, and CD36) in WAT. We also found that adipocyte hypertrophy, tumor necrosis factor-alpha (TNF-alpha) 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.
Guri
Amir J
AJ
Laboratory of Nutritional Immunology and Molecular Nutrition, Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, 319 Wallace Hall, Blacksburg, VA 24061, USA.
Hontecillas
Raquel
R
Si
Hongwei
H
Liu
Dongmin
D
Bassaganya-Riera
Josep
J
D000040:Abscisic Acid / Q000008:administration & dosage*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005951:Glucose Tolerance Test; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009765:Obesity / Q000150:complications; D047495:PPAR gamma / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D045162:Thiazolidinediones
D001786:Blood Glucose; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000040:Abscisic Acid