title: Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue.
abstract: Pyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti-inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome-induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)-induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome-mediated pyroptosis was also inhibited by melatonin in adipocytes. Further analysis revealed that gasdermin D (GSDMD), the key executioner of pyroptosis, was the target for melatonin inhibition of adipocyte pyroptosis. Importantly, we determined that nuclear factor κB (NF-κB) signal was required for the GSDMD-mediated pyroptosis in adipocytes. We also confirmed that melatonin alleviated adipocyte pyroptosis by transcriptional suppression of GSDMD. Moreover, GSDMD physically interacted with interferon regulatory factor 7 (IRF7) and subsequently formed a complex to promote adipocyte pyroptosis. Melatonin also attenuated NLRP3 inflammasome activation and pyroptosis, which was induced by LPS or obesity. In summary, our results demonstrate that melatonin alleviates inflammasome-induced pyroptosis by blocking NF-κB/GSDMD signal in mice adipose tissue. Our data reveal a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Zhenjiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Yatao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Luo
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ren
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Song
authors.initials: S
authors.lastname: Wu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi, China.
authors.forename: Chao
authors.identifier: http://orcid.org/0000-0001-7222-4028
authors.initials: C
authors.lastname: Sun
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism*; D028044:Phosphate-Binding Proteins; D000069292:Pyroptosis / Q000187:drug effects*; D000094524:Gasdermins
chemical_list: D051017:Apoptosis Regulatory Proteins; D058847:Inflammasomes; D047908:Intracellular Signaling Peptides and Proteins; D008550:Melatonin; D016328:NF-kappa B; D028044:Phosphate-Binding Proteins; C498368:Gsdmd protein, mouse; D000094524:Gasdermins
keywords: 
  GSDMD
  ; NF-κB; adipocyte; inflammasome; melatonin; pyroptosis