title: The role of caloric load and mitochondrial homeostasis in the regulation of the NLRP3 inflammasome.
abstract: Sterile inflammation is a cornerstone of immune activation in obesity and type 2 Diabetes Mellitus. The molecular underpinnings of this inflammation include nutrient excess-mediated activation of the innate immune NLRP3 inflammasome. At the same time, disruption of mitochondrial integrity is emerging as an integral control node in NLRP3 inflammasome activation and is also associated with caloric overload conditions including obesity and diabetes. Conversely, caloric restriction and fasting mimetic interventions alleviate these caloric excess-linked diseases and reduce inflammation and the NLRP3 inflammasome. The objective of this review is to integrate the findings linking mitochondrial integrity to the activation of the NLRP3 inflammasome and to evaluate how caloric restriction or caloric restriction mimetic compounds may play a role in attenuating the NLRP3 inflammasome and sterile inflammation.
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, 10-CRC, Room 5-3150, 10 Center Drive, Bethesda, MD, 20892-1454, USA.
authors.forename: Javier
authors.initials: J
authors.lastname: Traba
authors.affiliation: Cardiovascular and Pulmonary Branch, National Heart Lung and Blood Institute, NIH, 10-CRC, Room 5-3150, 10 Center Drive, Bethesda, MD, 20892-1454, USA. sackm@nih.gov.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Sack
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000473:pathology; D002149:Energy Intake; D006801:Humans; D058847:Inflammasomes / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D008928:Mitochondria / Q000276:immunology* / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000276:immunology*; D009765:Obesity / Q000276:immunology*; D037761:Sirtuins / Q000276:immunology
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D037761:Sirtuins
keywords: Mitochondria; NLRP3 inflammasome; Obesity; Sirtuins; Sterile inflammation