Zinc accumulation in macrophages exacerbates metabolic dysfunction-associated steatotic liver disease progression

{"Metabolic":[0],"dysfunction-associated":[1],"steatotic":[2],"liver":[3],"disease":[4,66],"(MASLD)":[5],"affects":[6],"over":[7],"1":[8],"billion":[9],"people":[10],"globally,":[11],"yet":[12],"the":[13,65,74,85,102,107,123,166,173],"role":[14,167],"of":[15,45,50,72,84,168],"trace":[16],"elements":[17],"in":[18,34,89,159,170,186],"its":[19],"progression":[20],"remains":[21],"poorly":[22],"defined.":[23],"Here,":[24],"we":[25,55],"identify":[26],"\\"macrophage":[27],"zinc":[28,32,39,59,80,86,100,169,184],"trapping\\"":[29],"(i.e.,":[30],"selective":[31],"accumulation":[33,185,191],"hepatic":[35,75],"macrophages":[36,76,131,187],"despite":[37],"systemic":[38,176],"depletion)":[40],"as":[41],"a":[42,48,69,206],"critical":[43],"driver":[44],"MASLD.":[46],"In":[47,68,95],"cohort":[49],"1069":[51],"individuals":[52],"with":[53,64,140],"MASLD,":[54,73,171],"found":[56],"that":[57,183],"serum":[58],"levels":[60],"were":[61],"inversely":[62],"correlated":[63],"severity.":[67],"mouse":[70,161],"model":[71],"are":[77],"marked":[78],"by":[79],"accumulation.":[81],"Macrophage-specific":[82],"depletion":[83],"exporter":[87],"Slc30a1":[88],"mice":[90],"recapitulates":[91],"human":[92],"MASLD":[93],"pathology.":[94],"macrophage-specific":[96],"Slc30a1-deficient":[97],"mice,":[98],"trapped":[99],"activates":[101],"Ire1α-Xbp1s":[103],"pathway,":[104],"which":[105],"on":[106,122],"one":[108],"hand":[109,125],"stimulates":[110],"IL-1β":[111,119,147],"secretion":[112],"to":[113,132,178],"alter":[114],"hepatocyte":[115,189],"lipid":[116,128,190],"metabolism":[117],"via":[118],"signaling,":[120],"and":[121,144,157,197,205],"other":[124],"enhances":[126],"direct":[127],"transfer":[129],"from":[130,175],"hepatocytes,":[133],"thereby":[134],"synergistically":[135],"exacerbating":[136],"steatosis.":[137],"Notably,":[138],"treatment":[139],"Ire1α":[141],"inhibitors":[142],"(4μ8C":[143],"STF-083010)":[145],"or":[146],"blockade":[148],"(clinically":[149],"approved":[150],"anti-IL-1β":[151],"antibodies)":[152],"reverse":[153],"established":[154],"steatosis,":[155],"inflammation,":[156],"fibrosis":[158],"preclinical":[160],"models.":[162],"This":[163],"work":[164],"redefines":[165],"shifting":[172],"paradigm":[174],"deficiency":[177],"cell-specific":[179],"sequestration.":[180],"It":[181],"reveals":[182],"exacerbates":[188],"through":[192],"both":[193],"fatty":[194],"acid":[195],"transflux":[196],"inflammation-driven":[198],"metabolic":[199],"reprogramming,":[200],"uncovering":[201],"novel":[202],"therapeutic":[203],"targets":[204],"clinically":[207],"actionable":[208],"biomarker.":[209]}