title: Apelin inhibits the activation of the nucleotide-binding domain and the leucine-rich, repeat-containing family, pyrin-containing 3 (NLRP3) inflammasome and ameliorates insulin resistance in severely burned rats.
abstract: BACKGROUND
  Hyperglycemia with insulin resistance remains a challenging problem in severely burned patients. Recent studies indicated the involvement of the nucleotide-binding domain and the leucine-rich, repeat-containing family, pyrin-containing 3 (NLRP3) inflammasome in insulin resistance and a beneficial role of apelin in insulin resistance. Our aim was to investigate whether apelin inhibits the activation of the NLRP3 inflammasome and ameliorates insulin resistance in severely burned rats.
  
  
  METHODS
  Male Wistar rats were subjected to a full-thickness burn injury comprising 40% of the total body surface area and were randomized to receive apelin, N(G)-methyl-L-arginine acetate salt (L-NMMA), and apelin plus treatments with L-NMMA. The following outcome measurements were assessed: apelin/APJ mRNA expression in white adipose tissue (WAT) and muscles, plasma apelin level, and activation of the NLRP3 inflammasome in WAT, Interleukin-1 β, interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1 levels in plasma, insulin resistance, survival rates, and endothelial nitric oxide synthase phosphorylation in soleus muscles.
  
  
  RESULTS
  Severe burn induced a decreased expression of apelin/APJ mRNA in soleus muscles and a decrease in plasma apelin levels. Burn injury with apelin treatment restored plasma apelin level, inhibited NLRP3 inflammasome activity in WAT, and decreased inflammatory cytokine levels in plasma. Rats treated with apelin also showed improved insulin sensitivity and decreased mortality, accompanied by a remarkable induction of endothelial nitric oxide synthase phosphorylation in soleus muscle. Furthermore, the aforementioned effects of apelin were inhibited in part by treatment with L-NMMA.
  
  
  CONCLUSIONS
  Apelin inhibits the activation of NLRP3 inflammasome, attenuates systemic inflammatory response, ameliorates insulin resistance, and promotes survival after severe burn, in part through an endothelial nitric oxide synthase-dependent pathway.
authors: Department of Burn and Plastic Surgery, The First Affiliated Hospital of PLA General Hospital, Beijing, China.
authors: Yunfei
authors: Y
authors: Chi
authors: Department of Burn and Plastic Surgery, The First Affiliated Hospital of PLA General Hospital, Beijing, China. Electronic address: cjkdoc@126.com.
authors: Jiake
authors: J
authors: Chai
authors: Department of Burn and Plastic Surgery, The First Affiliated Hospital of PLA General Hospital, Beijing, China.
authors: Chengfeng
authors: C
authors: Xu
authors: Department of Burn and Plastic Surgery, The First Affiliated Hospital of PLA General Hospital, Beijing, China.
authors: Hongmin
authors: H
authors: Luo
authors: Department of Burn and Plastic Surgery, The First Affiliated Hospital of PLA General Hospital, Beijing, China.
authors: Qinxue
authors: Q
authors: Zhang
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000073861:Apelin; D001665:Binding Sites; D002056:Burns / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002352:Carrier Proteins; D016207:Cytokines / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005951:Glucose Tolerance Test; D058847:Inflammasomes / Q000378:metabolism; D015601:Injury Severity Score; D007333:Insulin Resistance; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D007930:Leucine / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D000071198:Pyrin; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015996:Survival Rate
chemical_list: D000073861:Apelin; C498579:Apln protein, rat; D002352:Carrier Proteins; D016207:Cytokines; D003598:Cytoskeletal Proteins; D058847:Inflammasomes; D036341:Intercellular Signaling Peptides and Proteins; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat; D000071198:Pyrin; D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D007930:Leucine; D019331:NG-Nitroarginine Methyl Ester