Journal Article

Caprylic acid suppresses inflammation via TLR4/NF-κB signaling and improves atherosclerosis in ApoE-deficient mice

Xue, Changyong, Zhang, Xinsheng, Liu, Yinghua, Li, Feng, Xu, Qing, Li, Huizi, Guo, Changjiang, Zhang, Yong

2019

Overview

Background As reported previously by our group, medium-chain triglycerides can ameliorate atherosclerosis. Given that TLR4 is closely related to atherosclerosis, we hypothesized herein that caprylic acid (C8:0) would suppress inflammation via TLR4/NF-κB signaling and further promote the amelioration of atherosclerosis in apoE- deficient (apoE −/− ) mice. Methods Fifty 6-week male apoE −/− mice were randomly allocated into five diet groups: a high-fat diet (HFD) without or with 2% caprylic acid (C8:0), capric acid (C10:0), stearic acid (C18:0), or linolenic acid (C18:3). RAW246.7 cells were treated with caprylic acid (C8:0), docosahexenoic acid (DHA), palmitic acid (C16:0), and lipopolysaccharide (LPS) with or without TLR4 knock-down (TLR4-KD). The serum lipid profiles, inflammatory biomolecules, and mRNA and protein expression levels were measured. Atherosclerotic lesions that occurred in the aorta and aortic sinuses were evaluated and quantified. Results Our results indicated that C8:0 reduced body fat, improved the lipid profiles, suppressed inflammatory cytokine production, downregulated aortic TLR4, MyD88, NF-κB, TNF-α, IKKα, and IKKβ mRNA expression, and alleviated atherosclerosis in the apoE −/− mice ( P  < 0.05). In RAW 264.7 cells, C8:0 diminished the inflammatory response and both mRNA and protein expression of TLR4, MyD88, NF-κB, and TNF-α compared to those in the LPS and C16:0 groups ( P  < 0.05). However, in the TLR4-KD RAW 264.7 cells, C8:0 significantly upregulated NF-κB mRNA and protein expression compared to those in the C16:0 and DHA groups. Conclusions These results suggest that C8:0 functions via TLR4/NF-κB signaling to improve the outcomes of apoE −/− mice through suppressing inflammation and ameliorating atherosclerosis. Thus, C8:0 may represent as a promising nutrient against chronic inflammatory diseases.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Aorta / apoE-deficient mice / Apolipoprotein E / Arteriosclerosis / Atherosclerosis / blood lipids / Body fat / Caprylic acid / Cardiovascular disease / Clinical Nutrition / Coronary vessels / Cytokines / decanoic acid / Fatty acids / Gene expression / gene expression regulation / High fat diet / Inflammation / Inflammatory bowel disease / Inflammatory diseases / Insulin resistance / Linolenic acid / lipid composition / Lipopolysaccharides / males / Medicine / Medicine & Public Health / medium chain triacylglycerols / messenger RNA / Metabolic Diseases / mice / MyD88 protein / NF-κB protein / Octanoic acid / Oils & fats / Palmitic acid / protein synthesis / sinuses / Smooth muscle / Stearic acid / Systematic review / TLR4 / TLR4 protein / Toll-like receptor 4 / Toll-like receptors / transcription factor NF-kappa B / Triglycerides / tumor necrosis factor-alpha / Tumor necrosis factor-α