Open Journal http://dx.doi.org/10.17140/DROJ-3-e008 Diabetes Res Open J ISSN 2379-6375 DIABETES RESEARCH NLRP3 Infammasome Signaling Platform as New Pharmacological Target for Metafammation Debora Collotta, BSc; Massimo Collino, PhD * Department of Drug Science and Technology, University of Turin, Torino 10125, Italy Editorial * Corresponding author Massimo Collino, PhD Department of Drug Science and Technology University of Turin Via P. Giuria 9, Torino 10125, Italy Tel. +39 011 6706861 E-mail: massimo.collino@unito.it Article History Received: December 13 th , 2016 Accepted: December 16 th , 2016 Published: December 16 th , 2016 Citation Collotta D, Collino M. NLRP3 infam- masome signaling platform as new pharmacological target for Metafam- mation. Diabetes Res Open J. 2016; 3(1): e1-e3. doi: 10.17140/DROJ- 3-e008 Copyright ©2016 Collino M. This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Volume 3 : Issue 1 Article Ref. #: 1000DROJ3e008 Page e1 Metafammation is a metabolic infammatory state characterized by chronic, low- grade infammatory response initiated by excess nutrients in metabolic cells. 1 The infammatory signaling conducted by the metabolic cell eventually causes activation of specialized immune cells and leads to an unresolved infammatory response within the tissue. 2 The high level of co- ordination of infammatory and metabolic pathways is highlighted by the overlapping biology and function of macrophages and adipocytes in obesity. Preadipocytes under some conditions can exhibit phagocytic and antimicrobial properties and appear to even be able to differentiate into macrophages in the right environment, which suggests a potential immune role for preadi- pocytes. Furthermore, macrophages and adipocytes co-localize in white adipose tissue in obe- sity. Macrophages in adipose tissue are likely to contribute to the production of infammatory mediators either alone or in concert with adipocytes, which suggests a potentially important infuence of macrophages in promoting insulin resistance. Besides macrophages, obesity is as- sociated with aberrant expansion of other leukocytes (T-cells, B-cells, eosinophils, neutrophils and mast cells) in adipose tissue that contribute to chronic infammation. In particular, the increased neutrophils lead to a rise of myeloperoxidase (MPO) activity, a marker of neutrophil infltration, in the damaged tissue during infammation. 3 Despite the role of meta-infammation, in promoting metabolic diseases, including obesity and insulin resistance, is well known, 4 from a therapeutic perspective, only limited experience is available regarding the inhibition of spe- cifc infammatory pathways activated by the metabolic, biochemical and haemodynamic de- rangements known to exist in CMD. Thus, effective treatments that halt or induce regression of meta-infammation have potential to provide an immense clinical, social and economic beneft. Most recent evidences suggest a substantial role of the NLRP3 infammasome in regulating meta-infammation. The term “infammasome” was coined by Tschopp and co-workers in 2002 to describe a high-molecular-weight complex present in the cytosol of stimulated immune cells that mediates the activation of infammatory caspases. 5 To date, fve receptor proteins have been confrmed to assemble infammasomes, including the nucleotide-binding oligomerization domain (NOD), leucine-rich repeat (LRR)-containing protein (NLR) family members NLRP1, NLRP3 and NLRC4, as well as the proteins absent in melanoma 2 (AIM2) and pyrin. The best- characterized infammasome is the NLRP3 infammasome which interacts with an apoptosis- associated speck-like protein containing a caspase recruitment domain (ASC), thus recruiting and activating caspase-1. Because caspase-1 is an IL-1β-converting enzyme, it mediates the processing of pro-IL-1β into mature IL-1β and the consequent release of IL-1β, thereby caus- ing infammation. Yet, the induction of IL-1β release requires the transcriptional induction of pro-IL-1β. Thus, a system including pro-IL-1β induction and infammasome-mediated IL-1β maturation seems necessary for the regulation of this infammatory cytokine. The assembly of functional NLRP3 infammasome requires two distinct steps, priming and activation, re- spectively at the transcriptional and post-transcriptional levels. Furthermore, it is necessary to prime for a long time to increase the cellular expression of NLRP3 through NF-κB signal- ing. Post-transcriptional molecular mechanisms controlling NLRP3 activation that can respond quickly to stimuli without the need for NF-κB activation and new protein synthesis have also been identifed. Extracellular signal-regulated kinase 1 (ERK1)-mediated post-translational modifcations also permit the NLRP3 infammasome to respond to the second signal, ATP, by inducing post-translational events that are independent of any new production of pro-IL-1β or