sn-1,2-diacylglycerols protect against lethal endotoxemia by controlling systemic inflammation

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• Systemic inflammation is a key factor in multiple organ injuries and diseases.
• Diacylglycerols (DAG) are implicated in chronic inflammation, but their role in Toll-like receptor (TLR)-mediated inflammation is unclear.

Purpose of the Study:

• To investigate the mechanisms by which sn-1,2-diacylglycerols modulate lipopolysaccharide (LPS)/Toll-like receptor 4 (TLR4)-mediated inflammation.
• To determine the therapeutic potential of sn-1,2-diacylglycerols in systemic inflammatory diseases.

Main Methods:

• Enzyme-linked immunosorbent assay (ELISA) and western blotting were used to assess inflammatory markers in macrophages and endothelial cells.
• A murine model of LPS-induced systemic inflammation was employed to evaluate the in vivo effects of sn-1,2-diacylglycerols.
• Signaling pathways including p38 MAPK, PI3K/AKT, and NF-κB were analyzed.

Main Results:

• sn-1,2-diacylglycerols suppressed LPS-induced production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2) expression in a dose-dependent manner.
• In vivo, sn-1,2-diacylglycerols mitigated the "cytokine storm," reduced inflammatory mediator expression, and protected against LPS-induced lung damage and mortality.
• The mechanism involves the inhibition of LPS-induced p38 MAPK and PI3K/AKT-mediated NF-κB activation in macrophages.

Conclusions:

• Exogenous sn-1,2-diacylglycerol protects against LPS-induced lethal endotoxemia by suppressing TLR4-driven inflammatory responses.
• sn-1,2-diacylglycerols may represent a novel therapeutic strategy for systemic inflammatory diseases.
• 1,2-diacylglycerols hold potential as dietary health supplements for preventing or treating systemic inflammatory conditions.