Monounsaturated Fatty Acid-Enriched High-Fat Diets Impede Adipose NLRP3 Inflammasome-Mediated IL-1β Secretion and Insulin Resistance Despite Obesity
Monounsaturated Fatty Acid-Enriched High-Fat Diets Impede Adipose NLRP3 Inflammasome-Mediated IL-1β Secretion and Insulin Resistance Despite Obesity
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DOI：
10.2337/db14-1098
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发表时间：
2015-06-01
期刊：
影响因子：
7.7
通讯作者：
Roche, Helen M.
中科院分区：
文献类型：
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作者：
Finucane, Orla M.;Lyons, Claire L.;Roche, Helen M.
饱和脂肪酸（SFA）高脂饮食（HFD）可增强白细胞介素（IL）-1 β介导的脂肪炎症和胰岛素抵抗。然而，不同脂肪酸调节IL-1 β的机制以及随后对体内脂肪组织生物学和胰岛素敏感性的影响仍然难以捉摸。我们假设在HFD中用SFA代替单不饱和脂肪酸（MUFA）将减少脂肪组织中的pro-IL-1 β启动，并通过MUFA驱动的AMPK激活减弱胰岛素抵抗。与SFA-HFD-喂养的小鼠相比，MUFA-HFD-喂养的小鼠显示出改善的胰岛素敏感性，与减少的pro-IL-1 β引发、减弱的脂肪IL-1 β分泌和持续的脂肪AMPK活化一致。此外，MUFA-HFD-喂养的小鼠显示增生的脂肪组织，具有增强的基质血管组分的成脂潜力和改善的胰岛素敏感性。在体外，我们证明了MUFA油酸可以以AMPK依赖性方式阻止脂多糖和SFA引发的细胞中ATP诱导的IL-1 β分泌。相反，在回归研究中，从SFA-转换为MUFA-HFD未能逆转胰岛素抵抗，但改善了空腹血浆胰岛素水平。在人类中，高SFA消费者，但不是高MUFA消费者，显示降低胰岛素敏感性与升高pycard-1和caspase-1在脂肪组织中的表达。这些新的发现表明，饮食中的MUFA可以通过保存AMPK活性来减轻IL-1 β介导的胰岛素抵抗和脂肪功能障碍，尽管肥胖。
Saturated fatty acid (SFA) high-fat diets (HFDs) enhance interleukin (IL)-1 beta-mediated adipose inflammation and insulin resistance. However, the mechanisms by which different fatty acids regulate IL-1 beta and the subsequent effects on adipose tissue biology and insulin sensitivity in vivo remain elusive. We hypothesized that the replacement of SFA for monounsaturated fatty acid (MUFA) in HFDs would reduce pro-IL-1 beta priming in adipose tissue and attenuate insulin resistance via MUFA-driven AMPK activation. MUFA-HFD-fed mice displayed improved insulin sensitivity coincident with reduced pro-IL-1 beta priming, attenuated adipose IL-1 beta secretion, and sustained adipose AMPK activation compared with SFA-HFD-fed mice. Furthermore, MUFA-HFD-fed mice displayed hyperplastic adipose tissue, with enhanced adipogenic potential of the stromal vascular fraction and improved insulin sensitivity. In vitro, we demonstrated that the MUFA oleic acid can impede ATP-induced IL-1 beta secretion from lipopolysaccharide- and SFA-primed cells in an AMPK-dependent manner. Conversely, in a regression study, switching from SFA- to MUFA-HFD failed to reverse insulin resistance but improved fasting plasma insulin levels. In humans, high-SFA consumers, but not high-MUFA consumers, displayed reduced insulin sensitivity with elevated pycard-1 and caspase-1 expression in adipose tissue. These novel findings suggest that dietary MUFA can attenuate IL-1 beta-mediated insulin resistance and adipose dysfunction despite obesity via the preservation of AMPK activity.