Purinergic signaling modulates human visceral adipose inflammatory responses: implications in metabolically unhealthy obesity

[摘要] ObesityisaccompaniedbychronicinflammationofVAT,whichpromotesmetabolicchanges,andpurinergicsignalinghasakeyroleinawiderangeofinflammatorydiseases.Therefore,weaddressedwhetherfatinflammationcouldbedifferentiallymodulatedbythissignalingpathwayintheMUOandinindividualswhoremainMHO.OurresultsshowthatthenecrotizedVATofbothgroupsreleasedgreaterlevelsofATPcomparedwithleandonors.Interestingly,MUOtissueSVCsshowedup‐regulationandengagementofthepurinergicP2X7R.TheextracellularATPconcentrationisregulatedbyanenzymaticprocess,inwhichCD39convertsATPandADPintoAMP,andCD73convertsAMPintoadenosine.InVAT,theCD73ectoenzymewaswidelydistributedinimmuneandnonimmunecells,whereasCD39expressionwasrestrictedtoimmuneCD45PAN+SVCs.AlthoughtheMUOgroupexpressedthehighestlevelsofbothectoenzymes,nodifferenceinATPhydrolysiscapacitywasfoundbetweenthegroups.Asexpected,MUOexhibitedthehighestNLRP3inflammasomeexpressionandIL‐1βproduction.MUOSVCsalsodisplayedup‐regulationoftheA2AR,allowingextracellularadenosinetoincreaseIL‐1βlocalsecretion.Additionally,wedemonstratethatmetabolicparametersandBMIarepositivelycorrelatedwithpurinergiccomponentsinVAT.ThesefindingsindicatethatpurinergicsignalingisanovelmechanisminvolvedinthechronicinflammationofVATunderlyingthemetabolicchangesinobesity.Finally,ourstudyrevealsaproinflammatoryroleforadenosineinsustainingIL‐1βproductioninthistissue...

[学科分类] 生理学

[关键词] ATP;adenosine;inflammation