RRC ID 48889
Author Shen L, Yang Y, Ou T, Key CC, Tong SH, Sequeira RC, Nelson JM, Nie Y, Wang Z, Boudyguina E, Shewale SV, Zhu X.
Title Dietary PUFAs attenuate NLRP3 inflammasome activation via enhancing macrophage autophagy.
Journal J Lipid Res
Abstract Dietary PUFAs reduce atherosclerosis and macrophage inflammation, but how nucleotide-binding oligomerization domain leucine-rich repeat-containing receptor protein (NLRP3) inflammasome activation and autophagy influence PUFA-mediated atheroprotection is poorly understood. We fed Ldlr-/- mice diets containing 10% (calories) palm oil (PO) and 0.2% cholesterol, supplemented with an additional 10% of calories as PO, fish oil (FO), echium oil (EO, containing 18:4 n-3), or borage oil (BO, containing 18:3 n-6). Inflammasome activation, autophagic flux, and mitochondrial function were measured in peritoneal macrophages, blood monocytes, or liver from diet-fed mice. Compared with PO, dietary PUFAs (FO, EO, or BO) markedly inhibited inflammasome activation, shown by 1) less macrophage IL-1β secretion and caspase-1 cleavage in response to NLRP3 inflammasome activators, 2) less IL-1β secretion and caspase-1 cleavage from liver or hepatocytes in response to lipopolysaccharide (LPS), and 3) attenuated caspase-1 activity in blood monocytes. Furthermore, PUFA-enriched diets increased LC3-II expression in macrophage, aorta, and liver samples and reduced numbers of dysfunctional mitochondria in macrophages in response to LPS and palmitate, suggesting enhanced autophagic activation. Dietary PUFAs did not attenuate NLRP3 inflammasome activation in atg5-deficient macrophages, indicating that autophagic activation is critical for the PUFA-mediated inflammasome inactivation. In conclusion, dietary PUFAs reduce atherosclerosis, in part, by activation of macrophage autophagy and attenuation of NLRP3 inflammasome activation.
Volume 58(9)
Pages 1808-1821
Published 2017-9-1
DOI 10.1194/jlr.M075879
PII S0022-2275(20)33952-3
PMID 28729463
PMC PMC5580895
MeSH Animals Autophagy / drug effects* Caspase 1 / metabolism Dietary Fats / pharmacology* Enzyme Activation / drug effects Fatty Acids, Omega-3 / pharmacology* Fatty Acids, Omega-6 / pharmacology* Inflammasomes / metabolism* Liver / cytology Macrophages / cytology* Macrophages / drug effects Mice Mice, Inbred C57BL Mitochondria / drug effects Mitochondria / metabolism Monocytes / drug effects Monocytes / metabolism NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
IF 4.483
Times Cited 26
Mice RBRC02975