Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, 31008 Pamplona, Spain.
J Nutr Biochem. 2012 Mar;23(3):218-27. doi: 10.1016/j.jnutbio.2010.11.018. Epub 2011 Apr 14.
Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid with beneficial effects in obesity and insulin resistance. High levels of proinflammatory cytokine tumour necrosis factor-α (TNF-α) in obesity promote lipolysis in adipocytes, leading to the development of insulin resistance. Thus, the aims of the present study were to analyze the potential antilipolytic properties of EPA on cytokine-induced lipolysis and to investigate the possible mechanisms involved. The EPA effects on basal and TNF-α-induced lipolysis were determined in both primary rat and 3T3-L1 adipocytes. Treatment of primary rat adipocytes with EPA (100 and 200 μM) significantly decreased basal glycerol release (P<.01) and prevented cytokine-induced lipolysis in a dose-dependent manner (P<.001). Moreover, EPA decreased TNF-α-induced activation of nuclear factor-κB and extracellular-related kinase 1/2 phosphorylation. In addition, the antilipolytic action of EPA was stimulated by the AMP-kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-b-d-ribofuranoside and blocked by the AMPK-inhibitor compound C. Moreover, we found that EPA stimulated hormone-sensitive lipase (HSL) phosphorylation on serine-565, which further supports the involvement of AMPK in EPA's antilipolytic actions. Eicosapentaenoic acid treatment (24 h), alone and in the presence of TNF-α, also decreased adipose triglyceride lipase (ATGL) protein content in cultured adipocytes. However, oral supplementation with EPA for 35 days was able to partially reverse the down-regulation of HSL and ATGL messenger RNA observed in retroperitoneal adipose tissue of high-fat-diet-fed rats. These findings suggest that EPA inhibits proinflammatory cytokine-induced lipolysis in adipocytes. This effect might contribute to explain the insulin-sensitizing properties of EPA.
二十碳五烯酸（EPA）是一种ω-3 多不饱和脂肪酸，对肥胖和胰岛素抵抗具有有益作用。肥胖症中促炎细胞因子肿瘤坏死因子-α（TNF-α）水平升高可促进脂肪细胞的脂肪分解，导致胰岛素抵抗的发展。因此，本研究旨在分析 EPA 对细胞因子诱导的脂肪分解的潜在抗脂肪分解作用，并研究可能涉及的机制。在原代大鼠和 3T3-L1 脂肪细胞中，测定了 EPA 对基础和 TNF-α诱导的脂肪分解的影响。用 EPA（100 和 200 μM）处理原代大鼠脂肪细胞可显著降低基础甘油释放（P<.01），并呈剂量依赖性方式防止细胞因子诱导的脂肪分解（P<.001）。此外，EPA 降低了 TNF-α诱导的核因子-κB 和细胞外相关激酶 1/2 磷酸化的激活。此外，EPA 的抗脂肪分解作用被 AMP-激酶（AMPK）激活剂 5-氨基咪唑-4-甲酰胺-1-β-D-呋喃核糖苷刺激，并被 AMPK 抑制剂化合物 C 阻断。此外，我们发现 EPA 刺激激素敏感脂肪酶（HSL）在丝氨酸-565 上的磷酸化，这进一步支持 AMPK 参与 EPA 的抗脂肪分解作用。二十碳五烯酸处理（24 小时），单独和在 TNF-α存在下，还降低了培养脂肪细胞中脂肪甘油三酯脂肪酶（ATGL）的蛋白含量。然而，口服补充 EPA 35 天可部分逆转高脂肪饮食喂养大鼠腹膜后脂肪组织中观察到的 HSL 和 ATGL 信使 RNA 的下调。这些发现表明，EPA 抑制促炎细胞因子诱导的脂肪细胞脂肪分解。这种作用可能有助于解释 EPA 的胰岛素增敏特性。
