TLR2 inhibition ameliorates the amplification effect of LPS on lipid accumulation and lipotoxicity in hepatic cells
Open accessAbstract
BACKGROUND: -derived lipopolysaccharide (LPS) on lipid accumulation and lipotoxicity in palmitic acid (PA)-treated L02 cell as an NAFLD cell model, and the role of TLR2 in this process. METHODS: Oil red O staining assay and free fatty acid (FFA) content test were performed to determine the effects of LPS on lipid accumulation in a PA-induced NAFLD cell model with or without TLR2 inhibition. The levels of IL-6 and TNF-α were measured to investigate inflammation conditions. Hoechst 33342 staining assay and Caspase-3 activity assay were used to test cell apoptosis, and the expression levels of proteins in the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKKα/NF-κB signaling pathway, and mitochondrion-dependent apoptotic signaling pathway were detected using Western blot. RESULTS: Lipid accumulation, pro-inflammatory cytokine release, and cell apoptosis with high levels were observed in the PA-induced NAFLD cell model, and LPS aggravated these processes. Whereas TLR2 inhibition could significantly ameliorate PA-induced and LPS-amplified lipid accumulation, inflammatory, and cell apoptosis, it had no significant effect on L02 cells treated with LPS alone. CONCLUSIONS: These results were confirmed by activation or inhibition of the IRS1/PI3K/AKT signaling pathway, TLR2/MyD88/IKKα/NF-κB signaling pathway, and mitochondrion-dependent apoptotic signaling pathway, and were reflected by changes on their proteins expression. TLR2 is involved in PA-induced lipid accumulation and lipotoxicity in L02 cells, which could be aggravated by LPS, although LPS-induced amplification might not be through direct interaction with TLR2.
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TLR2 inhibition mitigates lipopolysaccharide-induced lipid accumulation in hepatic cells.
“In accordance, TLR2 inhibition has been shown to markedly mitigate lipopolysaccharide-induced lipid accumulation in hepatic cells (42).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [42]
The Results section reports that TLR2 inhibition markedly reduced lipid accumulation in palmitic-acid-treated L02 hepatic cells when LPS amplified that accumulation. The claim omits the palmitic-acid condition and can imply an effect on LPS-induced accumulation alone; the Results found no significant effect of TLR2 inhibition in cells treated with LPS alone. No page number is available in our copy. (LLM, conf=0.88)
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- Authors
- Zhang, L., Xie, Z., Yu, H., Du, H., Wang, X., Cai, J., Qiu, Y., Chen, R., Jiang, X., Liu, Z., Li, Y., & Chen, T.
- Affiliations
- Chinese Academy of Sciences (CN)
- Lanzhou University (CN)
- Fudan University (CN)
- Corresponding author
- Chen, Tuo
- Venue
- Annals of Translational Medicine
- Publisher
- AME Publishing Company
- Published
- 2021-09
- Volume
- 9
- Issue
- 18
- Pages
- 1429-1429
- ISSN
- 2305-5839 (ISSN-L)
- 2305-5847
- PMC
- PMC8506759
- OpenAlex
- W3203191581
- Cited by
- 12
- References
- 27
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 2
- FWCI
- 1.26
- Type
- journal article
- Language
- en
- Open access
- diamond
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Annals of Translational Medicine (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Lanzhou University Institutional Repository (submittedVersion)
- Funders
- Massachusetts Department of Agricultural Resources
- Lanzhou University
- National Natural Science Foundation of China (81360141, 81800528)
- Natural Science Foundation of Gansu Province (20JR5RA364)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- TLR2, lipopolysaccharide, non-alcoholic fatty liver disease, palmitic acid, hepatic lipid accumulation, lipotoxicity, mitochondrial apoptosis, inflammation, hepatocytes, L02 cells
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