Fessler Michael B, Rudel Lawrence L, Brown J Mark
Department of Pathology, Section on Lipid Sciences, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1040, USA.
Curr Opin Lipidol. 2009 Oct;20(5):379-85. doi: 10.1097/MOL.0b013e32832fa5c4.
Dietary saturated fatty acids (SFAs) have been implicated in promoting the metabolic syndrome and atherosclerotic cardiovascular disease. Recent evidence suggests that SFAs promote the metabolic syndrome by activating Toll-like receptor 4 (TLR4). Here we examine emerging molecular evidence that SFAs directly engage pathways of innate immunity, thereby promoting inflammatory aspects of the metabolic syndrome.
Accumulation of SFA in the body is tightly regulated by stearoyl-CoA desaturase 1, an enzyme that converts endogenous SFA to monounsaturated fatty acids. Recent studies have demonstrated that the accumulation of SFA seen with genetic deletion or inhibition of stearoyl-CoA desaturase 1 promotes inflammation, TLR4 hypersensitivity, and accelerated atherosclerosis. Therefore, stearoyl-CoA desaturase 1 may play an unexpected role in suppressing inflammation by preventing excessive accumulation of endogenous SFA-derived TLR4 agonists. In parallel, several independent laboratories have demonstrated that TLR4 is necessary for dietary SFAs to induce obesity, insulin resistance, and vascular inflammation in rodent models.
The metabolic syndrome and atherosclerotic cardiovascular disease have long been linked to dietary SFA intake and inflammation. Recent mechanistic insights into how SFAs and downstream metabolites can potentiate inflammation-driven metabolic disease are discussed here.
膳食饱和脂肪酸（SFA）与代谢综合征及动脉粥样硬化性心血管疾病的发生有关。最近的证据表明，SFA通过激活Toll样受体4（TLR4）促进代谢综合征。在此，我们研究新出现的分子证据，即SFA直接参与固有免疫途径，从而促进代谢综合征的炎症反应。
硬脂酰辅酶A去饱和酶1可将内源性SFA转化为单不饱和脂肪酸，从而严格调控体内SFA的蓄积。最近的研究表明，基因敲除或抑制硬脂酰辅酶A去饱和酶1后出现的SFA蓄积会促进炎症反应、TLR4超敏反应及加速动脉粥样硬化。因此，硬脂酰辅酶A去饱和酶1可能通过防止内源性SFA衍生的TLR4激动剂过度蓄积，在抑制炎症反应中发挥意想不到的作用。同时，多个独立实验室已证明，在啮齿动物模型中，TLR4是膳食SFA诱导肥胖、胰岛素抵抗及血管炎症所必需的。
长期以来，代谢综合征和动脉粥样硬化性心血管疾病一直与膳食SFA摄入及炎症反应有关。本文讨论了关于SFA及其下游代谢产物如何增强炎症驱动的代谢性疾病的最新机制见解。
