Obesity is featured by chronic systemic low-grade inflammation that eventually contributes to the development of insulin resistance. Toll-like receptor 4 (TLR4) is an important mediator that triggers the innate immune response by activating inflammatory signaling cascades. Human, animal and cell culture studies identified saturated fatty acids (SFAs), the dominant non-esterified fatty acid (NEFA) in the circulation of obese subjects, as non-microbial agonists that trigger the inflammatory response via activating TLR4 signaling, which acts as an important causative link between fatty acid overload, chronic low-grade inflammation and the related metabolic aberrations. The interaction between SFAs and TLR4 may be modulated through the myeloid differentiation primary response gene 88-dependent and independent signaling pathway. Greater understanding of the crosstalk between dietary SFAs and TLR4 signaling in the pathogenesis of metabolic imbalance may facilitate the design of a more efficient pharmacological strategy to alleviate the risk of developing chronic diseases elicited in part by fatty acid overload. The current review discusses recent advances in the impact of crosstalk between SFAs and TLR4 on inflammation and insulin resistance in multiple cell types, tissues and organs in the context of metabolic dysregulation.

肥胖的特征是慢性全身性轻度炎症，最终导致胰岛素抵抗的发展。Toll样受体4（TLR4）是一种重要的介质，可通过激活炎症信号级联反应来触发先天免疫应答。人类，动物和细胞培养研究确定，饱和脂肪酸（SFA）是肥胖受试者循环中的主要非酯化脂肪酸（NEFA），是通过激活TLR4信号传导触发炎症反应的非微生物激动剂。脂肪酸超载，慢性低度炎症和相关的代谢异常之间的重要因果关系。SFA和TLR4之间的相互作用可以通过髓样分化主要反应基因88依赖和独立的信号传导途径进行调节。在代谢失衡的发病机理中，对饮食中SFA和TLR4信号之间的串扰的更多了解可能有助于设计更有效的药理策略，以减轻部分由脂肪酸超负荷引起的发展为慢性疾病的风险。本综述讨论了在代谢失调的情况下，SFA和TLR4之间的串扰对多种细胞类型，组织和器官的炎症和胰岛素抵抗的影响的最新进展。