Neuroendocrine and cardiac metabolic dysfunction and NLRP3 inflammasome activation in adipose tissue and pancreas following chronic spinal cord injury in the mouse.
CVD (cardiovascular disease) represents a leading cause of mortality in chronic SCI (spinal cord injury). Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immuno-histochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin) and increased NPY (neuropeptide-Y) expression in the hypothalamic ARC (arcuate nucleus) and PVN (paraventricular nucleus), 1-month post-SCI. Long-form leptin receptor (Ob-Rb), JAK2 (Janus kinase)/STAT3 (signal transducer and activator of transcription 3)/p38 and RhoA/ROCK (Rho-associated kinase) signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome in VAT (visceral adipose tissue) and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.
*The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, U.S.A.
Gregory E
GE
Bigford
Valerie C
VC
Bracchi-Ricard
Robert W
RW
Keane
Mark S
MS
Nash
John R
JR
Bethea
D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D005260:Female; D007031:Hypothalamus / Q000378:metabolism / Q000503:physiopathology; D058847:Inflammasomes / Q000378:metabolism*; D053614:Janus Kinase 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009206:Myocardium / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009478:Neuropeptide Y / Q000378:metabolism; D010179:Pancreas / Q000378:metabolism* / Q000503:physiopathology; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D054411:Receptors, Leptin / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000503:physiopathology; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009478:Neuropeptide Y; C492716:Nlrp3 protein, mouse; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D011333:Pro-Opiomelanocortin; D053614:Janus Kinase 2; D020742:rhoA GTP-Binding Protein