Effects of delta-tocotrienol on obesity-related adipocyte hypertrophy, inflammation and hepatic steatosis in high-fat-fed mice

Effects of delta-tocotrienol on obesity-related adipocyte hypertrophy, inflammation and hepatic steatosis in high-fat-fed mice
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DOI:
10.1016/j.jnutbio.2017.07.003
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发表时间:
2017-10-01
影响因子:
5.6
通讯作者:
Moustaid-Moussa, Naima
Moustaid-Moussa, Naima
中科院分区:
医学2区
文献类型:
--
作者:
Allen, London;Ramalingam, Latha;Moustaid-Moussa, Naima

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炎症是肥胖相关代谢性疾病的主要潜在原因。因此,抗炎饮食成分可能会改善肥胖相关的疾病。我们推测,维生素E家族的成员--β-生育三烯醇(Delta-tocotrienol,Delta T3)可以通过其抗炎特性降低肥胖、胰岛素抵抗和肝甘油三酯。为了验证这一假设,C57BL/6J雄性小鼠被喂以高脂饮食(HF),并分别以400 mg/kg和1600 mg/kg的速度添加或不添加Delta T3(HF+Delta T3),持续14周,并与喂饲低脂饮食(LF)或HF添加二甲双胍的小鼠进行比较。糖耐量试验在治疗结束前2周进行。组织学、定量聚合酶链式反应和蛋白质分析用于评估脂肪和肝组织中的炎症和脂肪酸代谢。与HF组相比,补充Delta T3组的糖耐量显著改善,肝脏脂肪变性和血清甘油三酯减少。与其他组相比,HF+DeltaT3组的体重和脂肪垫重量没有明显减轻;但我们观察到,与其他组相比,他们的脂肪细胞体积更小,脂肪组织中的巨噬细胞浸润减少。这些变化至少部分是通过减少促炎症脂肪因子的mRNA和蛋白的表达以及增加抗炎脂肪因子的表达来解释的。此外,增量T3剂量依赖性地增加了脂肪组织和肝脏中脂肪酸氧化的标志物,减少了脂肪酸合成的标志物。总而言之,我们的研究表明,DeltaT3可能通过减少脂肪细胞肥大和减轻肝脏和脂肪组织的炎症来促进代谢健康的肥胖。(C)2017 Elsevier Inc.保留所有权利。
Inflammation is a major underlying cause for obesity-associated metabolic diseases. Hence, anti-inflammatory dietary components may improve obesity-related disorders. We hypothesized that delta-tocotrienol (delta T3), a member of the vitamin E family, reduces adiposity, insulin resistance and hepatic triglycerides through its anti-inflammatory properties. To test this hypothesis, C57BL/6j male mice were fed a high-fat diet (HF) with or without supplementation of delta T3 (HF+delta T3) at 400 mg/kg and 1600 mg/kg for 14 weeks, and they were compared to mice fed a low-fat diet (LF) or HF supplemented with metformin as an antidiabetic control. Glucose tolerance tests were administered 2 weeks prior to the end of treatments. Histology, quantitative polymerase chain reaction and protein analyses were performed to assess inflammation and fatty acid metabolism in adipose and liver tissues. Significant improvements in glucose tolerance, and reduced hepatic steatosis and serum triglycerides were observed in delta T3-supplemented groups compared to the HF group. Body and fat pad weights were not significantly reduced in HF+delta T3 groups; however, we observed smaller fat cell size and reduced macrophage infiltration in their adipose tissues compared to other groups. These changes were at least in part mechanistically explained by a reduction of mRNA and protein expression of proinflammatory adipokines and increased expression of anti-inflammatory adipokines in HF+delta T3 mice. Moreover, delta T3 dose-dependently increased markers of fatty acid oxidation and reduced markers of fatty acid synthesis in adipose tissue and liver. In conclusion, our studies suggest that delta T3 may promote metabolically healthy obesity by reducing fat cell hypertrophy and decreasing inflammation in both liver and adipose tissue. (C) 2017 Elsevier Inc. All rights reserved.