LeMieux Monique J, Kalupahana Nishan S, Scoggin Shane, Moustaid-Moussa Naima
Department of Nutritional Sciences, College of Human Sciences and Obesity Research Cluster, Texas Tech University, Lubbock, TX; and.
Department of Physiology, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
J Nutr. 2015 Mar;145(3):411-7. doi: 10.3945/jn.114.202952. Epub 2014 Dec 31.
Obesity is associated with an overexpansion of adipose tissue, along with increases in blood pressure, glycemia, inflammation, and thrombosis. Research to develop nutritional interventions to prevent or treat obesity and its associated diseases is greatly needed. Previously, we demonstrated the ability of eicosapentaenoic acid (EPA) to prevent high-fat (HF) diet-induced obesity, insulin resistance, and inflammation in mice.
The objective of the current study was to determine the mechanisms mediating the anti-inflammatory and antilipogenic actions of EPA.
In a previous study, male C57BL/6J mice were fed a low-fat diet (10% of energy from fat), an HF diet (45% of energy from fat), or an HF diet supplemented with EPA (45% of energy from fat; 36 g/kg EPA; HF+EPA) for 11 wk or an HF diet for 6 wk and then switched to the HF+EPA diet for 5 wk. In this study, we used histology/immunohistochemistry, gene expression, and metabolomic analyses of white adipose tissue from these mice. In addition, cultured mouse 3T3-L1 adipocytes were treated with 100 μM EPA for 48 h and then used for extracellular flux assays with untreated 3T3-L1 adipocytes used as a control.
Compared with the HF diet, the HF+EPA diet significantly reduced body weight, adiposity, adipocyte size, and macrophage infiltration into adipose tissue. No significant differences in overall body weight or fat pad weights were observed between HF-fed mice vs. those fed the HF+EPA diet for a short time after first inducing obesity with the HF diet. Interestingly, both histology and immunohistochemistry results showed a significantly lower mean adipocyte size and macrophage infiltration in mice fed the HF diet and then switched to the HF+EPA diet vs. those fed HF diets only. This indicated that EPA was able to prevent as well as reverse HF-diet-induced adipocyte inflammation and hypertrophy and that some of the metabolic effects of EPA were independent of body weight or adiposity. In addition, adipose tissue metabolomic data and cultured adipocyte extracellular flux bioenergetic assays indicated that EPA also regulated mitochondrial function by increasing fatty acid oxidation and oxygen consumption, respectively.
With the use of mice and cultured adipocytes, we showed that EPA ameliorates HF-diet effects at least in part by increasing oxygen consumption and fatty acid oxidation and reducing adipocyte size, adipogenesis, and adipose tissue inflammation, independent of obesity.
肥胖与脂肪组织过度扩张有关，同时伴有血压升高、血糖升高、炎症和血栓形成。迫切需要开展研究以开发预防或治疗肥胖及其相关疾病的营养干预措施。此前，我们已证明二十碳五烯酸（EPA）能够预防高脂（HF）饮食诱导的小鼠肥胖、胰岛素抵抗和炎症。
本研究的目的是确定介导EPA抗炎和抗脂肪生成作用的机制。
在之前的一项研究中，雄性C57BL/6J小鼠分别喂食低脂饮食（脂肪提供10%的能量）、HF饮食（脂肪提供45%的能量）或添加EPA的HF饮食（脂肪提供45%的能量；36 g/kg EPA；HF+EPA），持续11周；或者先喂食HF饮食6周，然后切换至HF+EPA饮食5周。在本研究中，我们对这些小鼠白色脂肪组织进行了组织学/免疫组织化学、基因表达和代谢组学分析。此外，将培养的小鼠3T3-L1脂肪细胞用100 μM EPA处理48小时，然后用于细胞外通量分析，未处理的3T3-L1脂肪细胞用作对照。
与HF饮食相比，HF+EPA饮食显著降低了体重、肥胖程度、脂肪细胞大小以及巨噬细胞向脂肪组织的浸润。在用HF饮食诱导肥胖后，短期喂食HF饮食的小鼠与喂食HF+EPA饮食的小鼠相比，总体重或脂肪垫重量未观察到显著差异。有趣的是，组织学和免疫组织化学结果均显示，与仅喂食HF饮食的小鼠相比，先喂食HF饮食然后切换至HF+EPA饮食的小鼠平均脂肪细胞大小和巨噬细胞浸润显著更低。这表明EPA既能预防又能逆转HF饮食诱导的脂肪细胞炎症和肥大，并且EPA的一些代谢作用独立于体重或肥胖程度。此外，脂肪组织代谢组学数据和培养的脂肪细胞外通量生物能量分析表明，EPA还分别通过增加脂肪酸氧化和氧气消耗来调节线粒体功能。
通过使用小鼠和培养的脂肪细胞，我们表明EPA至少部分地通过增加氧气消耗和脂肪酸氧化以及减少脂肪细胞大小、脂肪生成和脂肪组织炎症来改善HF饮食的影响，且独立于肥胖情况。
