A global perspective on the crosstalk between saturated fatty acids and Toll-like receptor 4 in the etiology of inflammation and insulin resistance. (January 2020)

• Record Type: Journal Article
• Authors: Li, Bin; Leung, Joseph C.K.; Chan, Loretta Y.Y.; Yiu, Wai Han; Tang, Sydney C.W.
• Is Part Of: Progress in lipid research. Volume 77(2020)
• Publication Date: 2020-01
• Subjects: ATF3 activating transcription factor 3 -- ACC1 acetyl-CoA carboxylase 1 -- AP1 activator protein 1 -- Akt protein kinase B -- ALT alanine aminotransferase -- AST aspartate aminotransferase -- BMDCs bone marrow-derived dendritic cells -- BMP4 bone morphogenetic protein 4 -- CCL C-C motif chemokine ligand -- CD cluster of differentiation -- CNS central nervous system -- COX2 cyclooxygenase 2 -- CVD cardiovascular disease -- CXCL C-X-C motif chemokine ligand -- DAMPs damage-associated molecular patterns -- DCs dendritic cells -- DIO diet-induced obesity -- eNOS endothelial nitric oxide synthase -- ER endoplasmic reticulum -- ERK extracellular signal-regulated kinase -- FAS fatty acid synthase -- GLUT4 glucose transporter 4 -- HFD high-fat diet -- HMGB1 high-mobility group box 1 -- HA hyaluronan -- IFNγ interferon γ -- ICAM intracellular adhesion molecule -- iNOS inducible nitric oxide synthase -- IKK inhibitory-κB kinase -- IκB inhibitory-κB -- IL interleukin -- INS2 insulin 2 -- IRAK interleukin 1 receptor-associated kinase -- IRF3 interferon regulatory factor 3 -- IRS1 insulin receptor substrate 1 -- JNK c-Jun N-terminal kinase -- LPS lipopolysaccharide -- MAPK mitogen-activated protein kinase -- MCP1 monocyte chemoattractant protein 1 -- MD2 myeloid differentiation factor 2 -- MHC major histocompatibility complex -- MIP1 macrophage inflammatory protein 1 -- MMP pro-matrix metalloproteinase -- MyD88 myeloid differentiation primary response gene 88 -- NADPH nicotinamide adenine dinucleotide phosphate -- NEFAs non-esterified fatty acids -- NF-κB nuclear factor-κB -- NO nitric oxide -- NOX4 NADPH oxidase 4 -- p38 p38 stress-activated protein kinase -- PAI1 plaminogen activator inhibitor 1 -- PAMPs pathogen-associated molecular patterns -- PDX1 pancreas and duodenum homeobox protein 1 -- PI3K phosphoinositide 3-kinase -- PPARγ peroxisome proliferator-activated receptor γ -- PRR pathogen recognition receptor -- ROS reactive oxygen species -- SAA serum amyloid A -- SCD1 stearoyl-CoA desaturase 1 -- SFAs saturated fatty acids -- siRNA small interfering RNA -- SOD2 superoxide dismutase 2 -- SOCS3 suppressor of cytokine signaling 3 -- STAT3 activator of transcription 3 -- T2DM type 2 diabetes mellitus -- TAK1 transforming growth factor β-activated kinase 1 -- TBK1 TRAF family member-associated NF-κB activator binding kinase 1 -- TIRAP Toll/interleukin 1 receptor domain-containing adaptor protein -- TLRs Toll-like receptors -- TNFα tumor necrosis factor α -- TRAF3 TNF receptor-associated factor 3 -- TRAF6 TNF receptor-associated factor 6 -- TRAM TRIF-related adaptor molecule -- TRIF Toll/interleukin 1 receptor domain-containing adaptor protein-inducing interferon β -- USFAs unsaturated fatty acids -- VCAM1 vascular cell adhesion molecule 1; Saturated fatty acids -- Toll-like receptor 4 -- Inflammation -- Insulin resistance -- Obesity -- Metabolic diseases; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2019.101020
• Languages: English
• ISSNs: 0163-7827

Abstract

Abstract: 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.