Dietary PUFAs attenuate NLRP3 inflammasome activation via enhancing macrophage autophagy

Area of Science:

• Cardiovascular Research
• Immunology
• Nutritional Science

Background:

• Dietary polyunsaturated fatty acids (PUFAs) are known to protect against atherosclerosis and reduce macrophage inflammation.
• The precise mechanisms by which PUFAs exert atheroprotective effects, particularly concerning NLRP3 inflammasome activation and autophagy, remain incompletely understood.

Purpose of the Study:

• To investigate the influence of dietary PUFAs on nucleotide-binding oligomerization domain leucine-rich repeat-containing receptor protein 3 (NLRP3) inflammasome activation and autophagy in the context of atherosclerosis.
• To elucidate the role of autophagy in mediating the atheroprotective effects of PUFAs.

Main Methods:

• Ldlr-/- mice were fed diets enriched with palm oil (PO), fish oil (FO), echium oil (EO), or borage oil (BO).
• Inflammasome activation, autophagic flux, and mitochondrial function were assessed in macrophages, monocytes, and liver tissues.
• Experiments included measuring IL-1β secretion, caspase-1 cleavage, LC3-II expression, and mitochondrial dysfunction.

Main Results:

• Dietary PUFAs (FO, EO, BO) significantly inhibited NLRP3 inflammasome activation compared to palm oil, evidenced by reduced IL-1β and caspase-1 cleavage in macrophages, liver, and monocytes.
• PUFA-enriched diets enhanced autophagic flux, indicated by increased LC3-II expression in various tissues and reduced dysfunctional mitochondria in macrophages.
• The inhibitory effect of PUFAs on NLRP3 inflammasome activation was dependent on autophagy, as it was not observed in atg5-deficient macrophages.

Conclusions:

• Dietary PUFAs confer atheroprotection partly through the activation of macrophage autophagy.
• PUFAs attenuate NLRP3 inflammasome activation, a key inflammatory pathway implicated in atherosclerosis.
• Autophagy is a critical mediator of the anti-inflammatory and atheroprotective actions of dietary PUFAs.