Dietary abscisic acid ameliorates glucose tolerance and obesity-related inflammation in db/db mice fed high-fat diets
Dietary abscisic acid ameliorates glucose tolerance and obesity-related inflammation in db/db mice fed high-fat diets
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DOI：
10.1016/j.clnu.2006.07.008
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发表时间：
2007-02-01
影响因子：
6.3
通讯作者：
Bassaganya-Riera, Josep
中科院分区：
文献类型：
--
作者：
Guri, Amir J.;Hontecillas, Raquel;Bassaganya-Riera, Josep
研究背景与目的：尽管噻唑烷二酮类药物(TZD)能有效改善胰岛素敏感性，但其副作用(如体重增加、肝毒性、充血性心力衰竭)限制了数百万糖尿病患者的应用。我们研究了一种与TZDS结构相似的天然植物化学物质脱落酸(ABA)是否可以替代TZDS来改善葡萄糖代谢。方法：我们首先考察了与TZDS类似的ABA是否在体外激活PPARγ。接下来，我们确定了饮食中ABA的最低有效剂量(100 mg/kg)，并评估了其对糖耐量、肥胖相关炎症以及高脂饮食db/db小鼠白色脂肪组织(WAT)中PPARγ及其反应基因mRNA表达的影响。结果：我们发现ABA在体外诱导了3T3-L1前脂肪细胞PPARγ的反式激活。补充36天的ABA可降低WAT大鼠的空腹血糖浓度，改善糖耐量，增加PPARγ及其反应基因(即脂联素、aP2和CD36)的mRNA表达。我们还发现，ABA喂养的小鼠WAT的脂肪细胞肥大、肿瘤坏死因子-α(TNF-α)的表达和巨噬细胞的浸润明显减少。结论：ABA可以作为一种营养干预措施来对抗2型糖尿病和肥胖相关的炎症。(C)2006年爱思唯尔有限公司和欧洲临床营养与代谢学会。版权所有。
Background Et 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 PPAR gamma 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 PPAR gamma 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 PPAR gamma 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 PPAR gamma 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. (c) 2006 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.