TLR4 overexpression enhances saturated fatty acid–induced inflammatory cytokine gene expression in sheep

Abstract

Saturated fatty acids (SFAs) can directly stimulate innate immune responses, thereby exacerbating inflammatory aspects of metabolic syndrome. Dietary SFAs act as ligands of Toll-like receptor 4 (TLR4), triggering associated signaling pathways. In this study, we investigated the role of TLR4 in palm oil SFA-associated inflammatory cytokine gene expression in monocytes/macrophages and adipose tissue using TLR4-overexpressing genetically modified sheep. SFA stimulation resulted in upregulation of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), interferon-γ (IFNγ), and interleukin-10 (IL-10), and TLR4 overexpression enhanced such SFA-induced inflammatory cytokine expression. Moreover, SFAs markedly activated MyD88-dependent signaling, including IL-1 receptor-associated kinase 4 (IRAK4), TNF receptor-associated factor 6 (TRAF6), and nuclear factor-κB (NF-κB). Taken together, our results indicate that TLR4 overexpression enhances the SFA-induced inflammatory response through MyD88-dependent signaling in monocytes/ macrophages and adipose tissue.

Evaluating the effect of TLR4-overexpressing on the transcriptome profile in ovine peripheral blood mononuclear cells

“…At the current statistical level, we found little difference in the overall gene expression levels between the Tg and WT libraries. The results of these analyses demonstrate that previous research of transgenic vector design and pronuclear microinjection are reliable for TLR4 overexpression [7,9,10,36].…”

“…Some studies have shown that genetic modification technology can be successfully applied for the prevention and control of diseases in chickens, cattle, and other animals [33][34][35]. In previous work, GM sheep with TLR4 overexpression were demonstrated to be effective against Gram-negative bacteria, and the growth performance, reproductive traits and offspring survivability of such sheep have also been researched and evaluated [7,9,10,36]. In the present study, Southern blot and real-time PCR were performed to verify the successful generating of TLR4-overexpressing sheep.…”

Anti-Inflammatory Function of Fatty Acids and Involvement of Their Metabolites in the Resolution of Inflammation in Chronic Obstructive Pulmonary Disease

“…TLR4 is an important participant in the immune response in COPD, as its function is to detect lipopolysaccharide (LPS) of Gram-negative bacteria. Only saturated fatty acids can activate TLR4, whereas unsaturated fatty acids do not [ 23 , 24 , 25 ]. These data emphasize the differential role of saturated and unsaturated fatty acids in inflammation [ 26 ].…”

Anti-Inflammatory Diet for Women with Interstitial Cystitis/Bladder Pain Syndrome: The AID-IC Pilot Study

“…Eating patterns that are high in saturated fat, cholesterol, protein, sugar, and salt coupled with regular consumption of ultra-processed foods are associated with a higher prevalence of chronic diseases with inflammatory components [ 28 ]. Studies suggest that dietary intake of saturated fat provokes inflammation by activating the Toll-like receptor (TLR)-4 cell-signaling pathways [ 33 , 34 ]. In a molecular dynamics study, it was found that the saturated fat palmitic acid (found in palm oil) produced TLR-4-induced changes to metabolism on a cellular level, as well as alterations in gene expression, lipid metabolic pathways, and membrane lipid composition.…”

“…Of note, Maserejian et al reported that modifying the dietary intake of the ratio of saturated fat to polyunsaturated fat may help control urinary urgency and frequency in women [ 37 ]. A potential link between diets high in saturated fat and IC/BPS symptomology emerges [ 30 , 33 , 34 , 35 , 36 ].…”