title: Therapeutic Opportunities in Damage-Associated Molecular Pattern-Driven Metabolic Diseases.
abstract: CONCLUSIONS
  Sterile inflammation is a common finding present in various metabolic disorders. This type of inflammation is mediated by damage-associated molecular patterns (DAMPs) that are released upon cellular injury to activate pattern recognition receptors on innate immune cells and amplify organ damage.
  
  
  BACKGROUND
  In the last decade, DAMPs, such as high-mobility group protein B1, nucleic acids (DNA, RNA), adenosine triphosphate, and other metabolites, were found to contribute to the inflammatory response in diabetes, gout, obesity, steatohepatitis, and atherosclerosis. Varied receptors, including Toll-like receptors (TLRs), the purinergic P2X(7) receptors, and nucleotide-binding domain, and leucine-rich repeat protein 3 (NLRP3)-inflammasome sense DAMPs and DAMP-like molecules and release the proinflammatory cytokines, interleukin (IL)-1β and IL-18.
  
  
  RESULTS
  Available therapeutic approaches that interfered with the signaling of TLRs, P2X(7), NLRP3-inflammasome, and IL-1β showed encouraging results in metabolic diseases, which will be also highlighted in this review.
  
  
  CONCLUSIONS
  It is important to understand the origination of DAMPs and how they contribute to the inflammatory response in metabolic disorders to develop selective and efficient therapeutics for intervention.
authors.affiliation: 1 Section of Digestive Diseases, Department of Internal Medicine, Yale University , New Haven, Connecticut.
authors.forename: Irma
authors.initials: I
authors.lastname: Garcia-Martinez
authors.affiliation: 1 Section of Digestive Diseases, Department of Internal Medicine, Yale University , New Haven, Connecticut.|2 Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University , Mansoura, Egypt .
authors.forename: Mohamed E
authors.initials: ME
authors.lastname: Shaker
authors.affiliation: 1 Section of Digestive Diseases, Department of Internal Medicine, Yale University , New Haven, Connecticut.
authors.forename: Wajahat Z
authors.initials: WZ
authors.lastname: Mehal
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects*; D053583:Interleukin-1beta / Q000378:metabolism; D008659:Metabolic Diseases / Q000188:drug therapy* / Q000276:immunology*; D058990:Molecular Targeted Therapy; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; D051193:Toll-Like Receptors