Journal
ANNALS OF TRANSLATIONAL MEDICINE
Volume 9, Issue 18, Pages -Publisher
AME PUBL CO
DOI: 10.21037/atm-21-4012
Keywords
Toll-like receptor 2; lipopolysaccharide (LPS); nonalcoholic fatty liver disease (NAFLD); lipid accumulation; inflammation
Categories
Funding
- National Natural Science Foundation of China [81360141]
- Postdoctoral Science Foundation of China [22019M653474]
- National Natural Science Foundation [81800528]
- Natural Science Foundation of Gansu Province [20JR0RA683, 20JR5RA364]
- Key Research and Development Project of Gansu Province [20YF2FA011]
- Health Industry Research Project in Gansu Province [GSWSKY2018-24]
- First Hospital of Lanzhou University [LDYYYN2018-41]
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The study revealed that TLR2 played a role in lipid accumulation and lipotoxicity in the PA-induced NAFLD cell model, which were aggravated by LPS. Inhibition of TLR2 significantly ameliorated these effects, while LPS alone had no significant impact on L02 cells.
Background: Gut microbiome dysbiosis is related to the pathogenesis of nonalcoholic fatty liver disease (NAFLD), and the role of toll-like receptor 2 (TLR2) in its molecular mechanism is controversial. Here, we investigated the effects and mechanisms of Escherichia coli-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-alpha 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/IKK alpha/NF-kappa B 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/IKK alpha/NF-kappa B 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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