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other·preclinical research, biomedical research, nutrition, cardiology·PMC10005197

Effects of Caprylic Acid and Eicosapentaenoic Acid on Lipids, Inflammatory Levels, and the JAK2/STAT3 Pathway in ABCA1-Deficient Mice and ABCA1 Knock-Down RAW264.7 Cells

Nutrients · 10 authors, 2 centres

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TL;DR

This preclinical study used ABCA1-deficient mice and knock-down cells to compare caprylic acid and EPA effects on lipids and inflammation, finding EPA superior in improving lipids and reducing inflammation via TLR4/NF-κBp65, while caprylic acid acted through ABCA1/JAK2/STAT3.

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Measurements included serum lipids (TG, TC, HDL-C, LDL-C), inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α, MCP-1), and gene/protein expressions via RT-PCR and Western blot. In aorta, C8:0 decreased p-STAT3 and p-JAK2 mRNA, EPA reduced TLR4 and NF-κBp65 mRNA.

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other

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preclinical research

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ORIGINAL PAPER

PMC10005197

Effects of Caprylic Acid and Eicosapentaenoic Acid on Lipids, Inflammatory Levels, and the JAK2/STAT3 Pathway in ABCA1-Deficient Mice and ABCA1 Knock-Down RAW264.7 Cells

Nutrients

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ABSTRACT

Our previous studies have found that caprylic acid (C8:0) can improve blood lipids and reduce inflammation levels and may be related to the upregulation of the p-JAK2/p-STAT3 pathway by ABCA1. This study aims to investigate the effects of C8:0 and eicosapentaenoic acid (EPA) on lipids, inflammatory levels, and the JAK2/STAT3 pathway in ABCA1-deficient mice (ABCA1 −/− ) and ABCA1 knock-down (ABCA1-KD) RAW 264.7 cells. Twenty 6-week ABCA1 −/− mice were randomly divided into four groups and fed a high-fat diet, or a diet of 2% C8:0, 2% palmitic acid (C16:0) or 2% EPA for 8 weeks, respectively. The RAW 264.7 cells were divided into the control or control + LPS group, and the ABCA1-KD RAW 264.7 cells were divided into ABCA1-KD with LPS (LPS group), ABCA1-KD with LPS + C8:0 (C8:0 group), and ABCA1-KD with LPS + EPA (EPA group). Serum lipid profiles and inflammatory levels were measured, and ABCA1 and JAK2/STAT3 mRNA and protein expressions were determined by RT-PCR and Western blot analyses, respectively. Our results showed that serum lipid and inflammatory levels increased in ABCA1 −/− mice ( p < 0.05). After the intervention of different fatty acids in ABCA1 −/− mice, TG and TNF-α were significantly lower, while MCP-1 increased significantly in the C8:0 group ( p < 0.05); however, LDL-C, TC, TNF-α, IL-6, and MCP-1 levels decreased significantly and IL-10 increased significantly in the EPA group ( p < 0.05). In the aorta of ABCA1 −/− mice, C8:0 significantly decreased p-STAT3 and p-JAK2 mRNA, while EPA significantly reduced TLR4 and NF-κBp65 mRNA. In the ABCA1-KD RAW 264.7 cells, TNF-α and MCP-1 were increased significantly and IL-10 and IL-1β were significantly decreased in the C8:0 group ( p < 0.05). The protein expressions of ABCA1 and p-JAK2 were significantly higher, and the NF-κBp65 was significantly lower in the C8:0 and EPA groups ( p < 0.05). Meanwhile, compared to the C8:0 group, the NF-κBp65 protein expression was significantly lower in the EPA group ( p < 0.05). Our study showed that EPA had better effects than C8:0 on inhibiting inflammation and improving blood lipids in the absence of ABCA1. C8:0 may be involved mainly in inhibiting inflammation through upregulation of the ABCA1 and p-JAK2/p-STAT3 pathways, while EPA may be involved mainly in inhibiting inflammation through the TLR4/NF-κBp65 signaling pathway. The upregulation of the ABCA1 expression pathway by functional nutrients may provide research targets for the prevention and treatment of atherosclerosis.

CITATION EXPORT

Xinsheng Zhang, Peng Zhang, Yinghua Liu et al.. Effects of Caprylic Acid and Eicosapentaenoic Acid on Lipids, Inflammatory Levels, and the JAK2/STAT3 Pathway in ABCA1-Deficient Mice and ABCA1 Knock-Down RAW264.7 Cells. Nutrients. (2023). https://doi.org/10.3390/nu15051296

AUTHORS

10 · 2 CENTRES

Xinsheng Zhang, Peng Zhang, Yinghua Liu, Zhao Liu, Qing Xu, Yong Zhang, Lu Liu, Xueyan Yang, Liya Li, Changyong Xue

1Department of Nutrition, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
2Guizhou Crops of Chinese People’s Armed Police Force, Guiyang 550001, China

EDITOR / REVIEWER

Maria Luz Fernandez, Andrea I. Doseff