Palmitic Acid Promotes Lung Metastasis of Melanomas via the TLR4/TRIF-Peli1-pNF-κB Pathway

Abstract

A high-fat diet plays an important role in aggravating cancers. Palmitic acid (PA) is one of the components of saturated fatty acids; it has been reported to promote tumor proliferation in melanomas, but the signal transduction pathway mediated by palmitic acid remains unclear. This study showed that palmitic acid can promote the lung metastasis of melanomas. Moreover, the interaction between palmitic acid and toll-like receptor 4 (TLR4) was predicted by molecular docking. The experimental results proved that palmitic acid could promote the TLR4 and Toll/IL-1 receptor domain-containing adaptor-inducing IFN-β (TRIF) expression. The expression of Pellino1 (Peli1) and the phosphorylation of NF-kappa B (pNF-κB) were downregulated after the suppression of TLR4 and the silencing of Peli1 also inhibited the phosphorylation of NF-κB. Therefore, we concluded that palmitic acid promoted the lung metastasis of melanomas through the TLR4/TRIF-Peli1-pNF-κB pathway.

IL-17A and PA synergistically promote the progression of melanoma by accelerating pATF2-CPT1A-mediated β-oxidation

“…Our Previous studies have shown that PA can promote the occurrence and development of melanoma [16] ; however, the underlying mechanism has not been fully elaborated. In the present study, we found that in a high PA environment, IL-17A helps PA to promote the metastasis of melanoma by targeting CPT1A with ATF2 (Figure 8).…”

The In Vitro, Ex Vivo, and In Vivo Effect of Edible Oils: A Review on Cell Interactions

“…Furthermore, the reproductive performance of rabbits was improved due to the (PUFA)-enriched diet [ 99 ]. On the other hand, palmitic acid derived from palm lung metastasis of melanomas, indicating the increased proliferation rate of the cells [ 98 ]. Furthermore, carcinogenesis and the role of fatty acids was investigated in female rats after consumption of sunflower, rapeseed, olive, or coconut oil.…”

A new frontier for fat: dietary palmitic acid induces innate immune memory

“…In contrast, oxidative phosphorylation in the mitochondria is upregulated, and the Krebs cycle remains intact, in order to support anti-inflammatory macrophage responses [19] . The plasticity of macrophage inflammatory polarization is governed by tightly regulated metabolic pathways that can be disrupted by excessive exposure to dietary SFAs, including PA [12,16,24] . PA is the most common SFA found in the human body (20%-30% total FAs) and is enriched in meat, dairy products (50%-60% of total fats), and is nearly 30% of total fats in breast milk [2,25] .…”

“…In contrast, oxidative phosphorylation in the mitochondria is upregulated, and the Krebs cycle remains intact, in order to support anti-inflammatory macrophage responses [ 19 ] . The plasticity of macrophage inflammatory polarization is governed by tightly regulated metabolic pathways that can be disrupted by excessive exposure to dietary SFAs, including PA [ 12 , 16 , 24 ] .…”

“…Specifically, enriched dietary palmitic acid ([PA]; C16:0), the most prevalent SFA found in the diet and circulating in human blood, has been shown to induce trained immunity within myeloid cells, and plays an important role in both homeostasis and infection in vivo [1,12,13] . PA is known to enhance toll-like receptor (TLR)-dependent inflammation by inducing ceramide metabolism, and sensitizes innate immune cells to subsequent TLR stimulation [12,[14][15][16] . During endotoxemia (lipopolysaccharide [LPS]-induced acute systemic shock), mice pre-exposed to PA exhibit enhanced circulating inflammation, disease severity, and mortality compared to vehicle (Veh)-treated mice and showed significantly greater clearance of fungal and bacterial infections compared to Veh-treated mice [12,13] .…”