Dietary PUFAs attenuate NLRP3 inflammasome activation via enhancing macrophage autophagy.

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.

• Authors: Lulu Shen, Yan Yang, Tiantong Ou, Chia-Chi C Key, Sarah H Tong, Russel C Sequeira, Jonathan M Nelson, Yan Nie, Zhan Wang, Elena Boudyguina, Swapnil V Shewale, Xuewei Zhu
• Journal: Journal of lipid research (J Lipid Res) Vol. 58 Issue 9 Pg. 1808-1821 (09 2017) ISSN: 1539-7262 [Electronic] United States
• PMID: 28729463 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Chemical References

• Dietary Fats
• Fatty Acids, Omega-3
• Fatty Acids, Omega-6
• Inflammasomes
• NLR Family, Pyrin Domain-Containing 3 Protein
• Caspase 1

Topics

• 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, drug effects)
• Mice
• Mice, Inbred C57BL
• Mitochondria (drug effects, metabolism)
• Monocytes (drug effects, metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (metabolism)