https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society r bs n bst rdsoe togyt diabetes to strongly diabetes predisposes with obesity women of and 70% obese and are men of 50% prevalence; Crepnigauthor: *Corresponding Abbreviations: syn- metabolic the dyslipidaemia, of components drome associated hyperglycaemia, other is and resistance, mass hypertension tissue insulin adipose with increased with Obesity Society g Nutrition the of Proceedings ise uha ie n kltlmsl nptet with patients between in in muscle link resistance skeletal causal insulin and liver and diabetes strong as mass a such tissue tissues adolescents clearly adipose and is children increased obese health there serious or Indeed, a overweight becoming in is issue diabetes 2 type Furthermore, el htpoueadrlaevrospoen termed proteins endocrine various active release also and are produce addition they in that function but cells storage TAG, store their that to cells insulin-sensitive are hmtci yoie,oeiyadtp diabetes: 2 type and obesity cytokines, Chemotactic hmatatn protein. chemoattractant dpcts h rdmnn eltp naioetissue, adipose in type cell predominant the Adipocytes, h uhr 09Frtpbihdoln 4Ags 2009 August 24 online published First 2009 Authors The https://www.cambridge.org/core etn fteNtiinScey otdb h ctihScin a eda h oa oit fEibrh Edinburgh Edinburgh, of Society Royal the at held was Section, Scottish the by hosted Society, Nutrition the of Meeting A (1,2) (5,6) nttt fCiia iceityadPtoiceity emnDaee etr Du Center, Diabetes German Pathobiochemistry, and Biochemistry Clinical of Institute ye2daee a akdyicesdin increased markedly has diabetes 2 Type . . C,ceoieC oi eetr ML1 hmkn-iercpo ;CC,ceoieCCmtflgn;MP monocyte MCP, ligand; motif CXC chemokine CXCL, 1; receptor chemokine-like CMKLR1, receptor; motif CC chemokine CCR, isedrvdceoatcctknsadterfnto nislnresistance insulin in function adipose of of their recruitment role insulin-sensitive the and the of vitro in evidence in cytokines beyond experimental homeostasis of to chemotactic activity glucose summary a and mass biological tissue-derived provides adipogenesis review tissue possess present on adipose The proteins this effects tissues. in increased these including role in linking cells of important tissue immune an factor many adipose play important of as may state adipokines most situation, inflammatory chemoattractant intensively the Furthermore, The of concept resistance. be years. state insulin a recent may chronic and in tissue, a patients obesity biology adipose to obese tissue in in linked adipose research directly infiltration in biomedical be macrophage studied may for tissue and adipokines and inflammation Adipose of biology low-grade class which proteins. tissue This chemerin, adipose with and chemotactic diseases. chemokines for associated obesity-related many diabetes. includes targets is including 2 proteins also diabetes interesting type chemotactic with are of which as range patients tissues such wide adipokines, and a in disorders patients releases of resistance obesity-related obese insulin secretion in in and exists mass altered mass muscle tissue tissue skeletal adipose adipose and Increased increased liver between as link such causal strong A . https://doi.org/10.1017/S0029665109990218 rfso Ju Professor ypsu n‘rnir naioetsu biology’ tissue adipose in ‘Frontiers on Symposium vdnefrapsil aslcorrelation? causal possible a for evidence . . IPaddress: hmkn:Ceei:Islnrssac:Aioetsu:Obesity tissue: Adipose resistance: Insulin Chemerin: Chemokine: ¨ gnEkl fax Eckel, rgen (2009), 170.106.33.19 68 erk eladJu and Sell Henrike 7–8 doi:10.1017/S0029665109990218 378–384 , + 9213867 mi [email protected] email 3382697, 211 49 , on 29 Sep2021 at12:17:59 n7ad8Arl2009 April 8 and 7 on (4) (3) . . ihatrdsceino dpkns h otipratof important TNF most associated the be are adipokines, to which of found secretion been altered has with diabetes patients with obese in patients mass and tissue adipose Increased adipokines. dps isems oislnrssac,adchemo- this in and role resistance, important an insulin play to might adipokines obese mass attractant increased recent in linking been tissue factor tissue in important has adipose adipose most biology the of be that may state tissue patients concept inflammatory adipose The a in years. tissue, studied macrophage adipose intensively a and to in inflammation linked dis- low-grade directly infiltration be of obesity-related may state adipokines and as chronic of well obesity class as This in biology eases. tissue increasingly research adipose becoming to biomedical are relation includ- in which proteins interesting chemotactic chemokines, of many range ing wide a releases also ¨ , subjectto theCambridgeCore termsofuse,available at gnEckel rgen * a L6adadiponectin and IL-6 , nvivo in nvivo in ¨ slof Germany sseldorf, and and (7) dps tissue Adipose . nvitro in https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society C- CL)Icesdi bst n ibtsChristiansen References diabetes and obesity in Increased diabetes 2 type and obesity to related data Clinical (CCL2) MCP-1 cytokine Chemotactic ufml fceoie,teaiotria cysteine main amino-terminal other the the adjacent chemokines, are chemokines, residues CC by of In separated acid. subfamily residues amino cysteine one only amino-terminal chemokines two CXC have residues. cysteine highly-conserved four C- CL3 lvtdi bst Hashimoto Kim Chavey of Huber resis- summary insulin in Jiao a function tance tissue-derived their adipose and provides of proteins role chemoattractant review the to of related evidence not present but experimental interferon obesity The kDa in 10 Increased IP-10, ligand; scenario. motif Herder CXC chemokine CXCL, ligand; motif CC resistance chemokine insulin CCL, with and protein; associated chemoattractant obesity not diabetes monocyte Linking but and MCP, obesity obesity in in Increased Increased Chemerin obesity in Elevated with associated (CXCL10) not IP-10 but obesity (CXCL8) in obesity IL-8 Increased in Elevated obesity CXCL5 in Elevated (CCL13) MCP-4 diabetes with Associated (CCL11) Eotaxin (CCL8) MCP-2 (CCL7) MCP-3 (CCL5) RANTES oteeptooisMP1i n ftems studied most adipose the of depots of different one patients is obese MCP-1 In chemokines. pathologies these to n atr hw ob novdi bst n obesity- and obesity in involved structurally be pathologies adipokines not to related the shown is comprise factors family, but and chemokine any cells to attract dendritic to related shown been and has which macrophages chemerin, as such proteins ec hmkn ciaigoeo oetre cell target more or one activating mono- types) as chemokine eosinophils small or such basophils are (each cells lymphocytes, immune T Chemokines neutrophils, various tissue. cytes, attract adipose that cell other in proteins or adipocytes residing from 1) related secreted (Table types adipokines diabetes be be 2 to type to and and shown obesity syndrome, been chemokine metabolic the have of those family, particularly proteins, Chemotactic discussed. also are cytokines chemotactic that to and related and inflammation be may tissue tissue obesity-related adipose of underlie adipose Mechanisms that diabetes. disorders from 2 type released and obesity being cytokines chemo- and tactic chemokines the between relationships known of htpasarl ntercuteto ooye n T and infection monocytes and of injury recruitment of the sites family in cytokine to role inducible lymphocytes small a the plays of that member a and kine lsaMP1lvl r akdyhge nobese in higher 2. markedly (CCR) are receptor motif levels patients CC MCP-1 chemokine Plasma the is receptor hmtci rtisi bst n ye2diabetes 2 type and obesity in proteins Chemotactic ooyeceotrcatpoen(C)1i chemo- a is (MCP)-1 protein chemoattractant Monocyte nvivo in (8) https://www.cambridge.org/core (11,12) hmknsaecaatrzdb h rsneof presence the by characterized are Chemokines . and al 1. Table n ainswt diabetes with patients and nvitro in (9) . (8) . lncldt hwn h soito ewe hmtci yoie n bst n ye2diabetes 2 type and obesity and cytokines chemotactic between association the showing data Clinical https://doi.org/10.1017/S0029665109990218 nadto,ohrchemoattractant other addition, In . h i st rvd noverview an provide to is aim The . ye2diabetes 2 type resistance insulin resistance insulin . IPaddress: 170.106.33.19 hmtci yoie,oeiyadtp ibts379 diabetes 2 type and obesity cytokines, Chemotactic (13) n nrelation in and , nvivo in (10) , on t main Its . 29 Sep2021 at12:17:59 othe to oetsu hwicesdepeso fMCP-1 of expression adi- increased epicardial and show subcutaneous tissue visceral, pose as such tissue cise ibtsi ag emnsuychr,etxni not is eotaxin cohort, study resistance 2 German insulin type large with with associated associated a be While in to as fat. found diabetes patients been subcutaneous also obese and has of controls RANTES lean tissue with adipose compared visceral in expressed oehrwt nicesdepeso ftecorresponding patients the expression obese of in in expression receptors increase increased marked an a with together shown has tissue adipose of levels decreased show surgery MCP-1 bariatric after weight lose uaeu iseadi lsl eae otenme of number the sub- to in related than closely tissue macrophages been is adipose resident and visceral has tissue in MCP-1 higher cutaneous be of to Expression found MCP-1 concentrations. reduce patients, plasma obese in sensitivity insulin improve ecie lncl eaoi n muooia risk immunological and previously- of metabolic factors independently clinical, risk described diabetes to contribute htptet ihtp ibtsdslyeeae MCP-1 elevated display diabetes as demonstrated 2 have levels type resistance, relationship studies with Several insulin patients a diabetes. that and 2 for type levels as evidence well MCP-1 good serum provide between data Clinical nlrto naioetissue adipose in infiltration ewe ihrlvl fI- noeiyadincreased the diabetes and as established, and obesity fully IL-8 been in between yet association IL-8 not has of resistance insulin levels higher between 3ad- u ti la htteeaioie r elevated are adipokines these that clear patients is obese it in but -4 and -3 L8i ertdfo dps iseadispam levels obesity plasma its in and tissue increased adipose chemokines. CXC from are are secreted 10) is (CXCL) IL-8 ligand motif CXC kine iad1)aeas lvtdi h eu foeepatients controls obese of motif lean serum CC with the chemokine in compared (or elevated as also eotaxin are and 11) 5) ligand ligand motif CC ee aaaeaalbefrohrMPsc sMCP-2, as such MCP other for available are data Fewer L8ad1 D interferon kDa 10 and IL-8 te Cceoie uha ATS(rchemokine (or RANTES as such chemokines CC Other , subjectto theCambridgeCore termsofuse,available at (18) (13,16,17) (13) pioglitazone , (20) Bozaoglu Herder Hashimoto ovrey ibtstetet uha exer- as such treatments diabetes Conversely, . Simeoni Malavazos rbbyi aallwt oe macrophage lower with parallel in probably , tal et tal et ihMP1lvl aebe hw to shown been have levels MCP-1 High . tal et tal et tal et tal et . . (12) (25) (15,23–25) tal et tal et . tal et tal et (15) . . (26,31) (26) Herder , . tal et (32) tal et . (19) Murdolo , (9) . (21) . . (17) (23) (23) . . (11) (14) esrmn fteefcosin factors these of Measurement . that patients obese Conversely, . n egtloss weight and Vasudevan , (28–30) (15) Kim , tal et Huber , (22) . g tal et . . idcdpoen(rchemo- (or protein -induced (13) tal et oee,acorrelation a However, . (23,26,27) (26) . tal et (24) . (12) . tal et . (15) (13) Herder , oai sover- is Eotaxin . . g (27) Piemonti , (20) idcdprotein. -induced satnae by attenuated is l fwhich of all , tal et . tal et (13) (14,15) , . (16) , . https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society erto shgl euae naioye,ie increased i.e. adipocytes, in regulated highly is secretion rti r nrae noeeptet u r o asso- not resistance are but insulin patients with obese in ciated increased are protein C-,frwihislnrssac-nuigcpct is capacity resistance-inducing as insulin which such postulated which cells, chemokines for tissue-derived immune adipose MCP-1, of to biological recruitment applies possess also the to beyond shown been activity have chemokines Many hmrnYsIdcsislnrssac naioye Kralisch insulin- adipocytes in are resistance insulin Induces Skurk who in individuals increased Vasudevan from Chavey markedly interferon- insulin by cells is induces Regulated demon- and resistant adiponectin expression fat has by Regulated IL-8 study human Another that factors. and strated metabolic muscle risk other skeletal and in immunological BMI resistance insulin for Induces adjustment multivariable Yes adipocytes visceral GRO- in 1; Increased protein inflammatory macrophage MIP-1, ligand; motif CC fraction) chemokine (SV CCL, Yes Eckel Yes protein; J. chemoattractant monocyte obesity and MCP, in Sell Yes release H. Increased Chemerin (CXCL10) IP-10 fraction) (SV Yes (CXCL8) IL-8 Yes CXCL5 GRO- (CCL11) Eotaxin (CCL5) RANTES MIP-1 MIP-1 380 eti akdyicesdlvl noeesbet as subjects obese in pre- is levels controls that lean increased adipokine with new markedly compared a in be to sent revealed been recently ye nrodents in cytes C- CL)YsLne oislnrssac nmuemodels, mouse in resistance insulin to Linked Yes Adipokine (CCL2) MCP-1 cytokine Chemotactic lohgl xrse naioetissue adipose are in ChemR23) expressed (or highly (CMKLR1) also 1 receptor chemokine-like ainbtenceei eesadBI lo A and TAG blood BMI, corre- and pressure a levels blood despite chemerin patients between control lation between and levels diabetes chemerin with in patients difference no is there However, rti.Iiilydsoee nbd ud associated fluids body in processes inflammatory discovered with chemoattractant Initially secretory a protein. chemerin, chemokine include to this expanded reduction. of weight after concentration subjects obese serum in the decreases that shown htaioye nyprl otiuet h C- output MCP-1 tissue the adipose to contribute from partly only adipocytes that dpctsrlaehge eeso C- oehrwith together MCP-1 cytokines of pro-inflammatory levels other higher release adipocytes bst n ye2daee)cmae ihcontrols with compared diabetes) 2 of type tissue and adipose obesity in elevated is diabetic chemerin that shown have toavsua;CC,ceoieCCmtflgn;I-0 0kainterferon kDa 10 IP-10, ligand; motif CXC chemokine CXCL, vascular; stroma eety h ail-rwn dpkn aiyhas family adipokine rapidly-growing the Recently, hmtci dpkns aafo nmlmodels animal from data adipokines: Chemotactic https://www.cambridge.org/core a b a CL)YsRgltdb dpnci n nue of inducer and adiponectin by Regulated Yes (CCL4) CC1 e euae yaioetnDietze-Schroeder adiponectin by Regulated Yes (CXCL1) CL)YsRgltdb dpnci Gerhardt adiponectin by Regulated Yes (CCL3) (30) smoy obesus Psammomys (35,36) eu eeso 0kainterferon kDa 10 of levels Serum . al 2. Table (9) Tbe2.MP1i ertdfo adipo- from secreted is MCP-1 2). (Table . (35,37) . https://doi.org/10.1017/S0029665109990218 (40) n elculture cell and nvitro In . n ua subjects human and nvitro In . IPaddress: (33) (32) vdneta hmtci yoie r dpknswt osberl nislnresistance insulin in role possible a with adipokines are cytokines chemotactic that evidence sn a;a nmlmdlof model animal an rat; (sand hmrnadisreceptor its and chemerin , h aesuyhsalso has study same The . (26,31) C- xrsinand expression MCP-1 , (39) 170.106.33.19 tapas however, appears, It . XL a very has CXCL5 . (9,34) nvitro In . (11,38) , on nvivo In nui eitnei kltlmsl cells muscle skeletal in resistance insulin eitnei kltlmsl cells muscle skeletal in resistance dpctsadseea ucecells muscle skeletal and adipocytes vdnefrarltosi ihislnrssac References resistance insulin with relationship a for evidence 29 Sep2021 at12:17:59 g -induced Large . data (9) . g idcdprotein. -induced yisln TNF insulin, by faioetissue independently adipose and of and dependently homeostasis both glucose markers improve inflammatory to shown been has CCR2 itidcdoeemc rihbto fMP1expression in MCP-1 of deficiency inhibition in MCP-1 or mice overexpression, obese diet-induced MCP-1 to contrast a 1 protein inflammatory irtdiflmaoypol oehrwt eue insulin reduced con- with ame- lacking resistance together decreased an profile and is is inflammatory number CCR2 liorated macrophage obesity reduced when diet-induced with that comitantly of found efficiency has the however, study, rvn bst nue yahg-a diet high-fat its a for by case induced not does the obesity signalling MCP-1 also prevent has of mice is disruption CCR2-knock-out that with which demonstrated study One understood, CCR2. fully receptor not is htMP1dfiinyde o eueobesity-induced tissue reduce suggest adipose not group in does another inflammation deficiency from MCP-1 data that conflicting hand, other h ubro arpae naioetissue adipose in macrophages of number the nedciemne nseea muscle has in skeletal MCP-1 in sensitivity manner insulin of endocrine reduce an can overexpression MCP-1 tissue that demonstrated adipose with mice pae niaigta hsctkn a otiueto contribute may resistance cytokine insulin glucose of this impairs pathogenesis that the MCP-1 treat- with indicating Conversely, adipocytes patients. uptake, 3T3-L1 obese of in ment increased are which eeso C- nuerbs nui resistance insulin robust an hypophysiological induce even MCP-1 in that skeletal of shown human only levels been has primary acting it In cells manner. by muscle paracrine resistance or insulin autocrine cause however, ie taoi,wihocr nteasneo n increase any of absence weight the body and in insulin can in occurs tissue as which alone adipose such steatosis, into liver obesity tissue infiltration diet-induced macrophage adipose of resistance, effects in the MCP-1 mimic of overexpression , subjectto theCambridgeCore termsofuse,available at g n L8i niie yadiponectin by inhibited is IL-8 and h ees fteceoie C-,macrophage MCP-1, chemokines the of release The hs h oeo C- naioetsu inflammation tissue adipose in MCP-1 of role the Thus, h s fmuemdl a eeldta specific that revealed has models mouse of use The db/db (46) ieaeirtsislnrssac n reduces and resistance insulin ameliorates mice utemr,pamclgclihbto of inhibition pharmacological Furthermore, . (42) (47,48) a h aesuyhsas hw htin that shown also has study same The . rwhhroeadIL-6 and hormone growth , . a and b Sell Herder Sell Sell rwhrgltdoncogene growth-regulated , a Dietze-Schroeder Dietze-Schroeder Dietze-Schroeder Kanda rwhrgltdoncogene growth-regulated , (43) tal et tal et tal et tal et nte td using study Another . tal et tal et tal et . . . (35) tal et (36) (36) (36) tal et (38) . (73) . tal et (44) , , Gerhardt , (76) . C- osnot, does MCP-1 . . (32) dpnci sa is Adiponectin . (55) . . (42) Madani , (37) . . (27) Kamei , , tal et (45) (42) tal et al et tal et (41) Another . . (36) (38) tal et nthe On . tal et . . . l of all , (38) (38) (38) tal et . . . a (37) (75) SV, ; . (44) , https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society et nui eitnei yctsudron co-culture by pre- undergoing adipocytes and myocytes simultaneously with in secretion adipokines resistance adipocyte insulin of vents release of the regulator decreasing autocrine an as h rgno hmrni h ie,ln n other and lung liver, the and in Concentrations chemerin chemokine. of this chemerin origin of adipocyte-derived levels the of serum contribution to overall the lnclsuyhsdmntae ikbtenhigh between one link but a adiponectin, hypoadiponectinaemia by and demonstrated regulated levels has is eotaxin data no study it are there that clinical eotaxin of suggest case the to In diabetes. 2 type and rmnn dpkn hti erae noeiyadthat sensitivity and obesity insulin in influences decreased is positively that adipokine prominent ei xrsini o nrae naioetsu of tissue adipose in che- increased that reveals not mice diabetes is genetically-obese and expression obesity merin of models animal ldn L8 arpaeiflmaoypoen1 protein inflammatory macrophage IL-8, cluding pert etemjrsuc fti chemokine this of source cells major vascular the stroma be but to tissue appear adipose from released also dps isecl ye oceei rdcin thas CMKLR1 It express responsive production. macrophages chemerin various chemerin are that and of to demonstrated types contribution been cell stroma a the tissue in suggesting adipose found be fraction, regu- also up can vascular chemerin is tissue which adipose In of TNF secretion by the lated chemerin, of amounts niaoso nui eitneadtedvlpetof development the and resistance diabetes insulin good are of obesity in indicators observed levels adiponectin plasma low inicesswt adipogenesis with increases sion ihri bs insulin-resistant obese in higher oepoone nraei ML1ta nche- in than CMKLR1 CMKLR1 in shows increase and differentiation pronounced merin chemerin after more and of a before expression comparison mRNA a adipocytes lo hmrnlvl n M hti needn of independent is that BMI and tolerance between glucose levels correlation a chemerin reported has blood subjects human in study svrlkokono xrsino ohpoen com- proteins both process of this expression inhibits of pletely knockdown viral as 2 receptor of point. motif role this CXC the at chemokine discuss definitively other receptor to its by difficult of and verification phenotypes is CXCL5 varying it need the one mice results of by CCR2-knock-out light these studied in so been Furthermore, studies. only far, has so CXCL5 group should that res- It mentioned mice. insulin wild-type be motif enhanced with compared CXC display when chemokine ponsiveness mice Also, 2-knock-out intake. changing motif food without receptor CXC or sensitivity weight chemokine insulin body improves receptor, 2, corresponding antagonist receptor an the or insulin-resistant antibody anti-CXCL5 for in an either signalling using mice CXCL5 tissue In adipose tissues. blocking between peripheral in addition, link resistance resis- a insulin adipose to insulin and inflammation pointing of induces muscle, chemokine fraction in this tance macrophage MCP-1 the Like tissue. by secreted mainly C-,idc nui eitnei kltlmuscle skeletal in resistance insulin cells induce MCP-1, XL,avr eetadto oteadipokines the to addition recent very a CXCL5, hmrnadCKR r eesr o adipogenesis, for necessary are CMKLR1 and Chemerin (36) (34) https://www.cambridge.org/core (50) n hrb a ersn ikbtenobesity between link a represent may thereby and ua dpctsas ees measurable release also adipocytes Human . thsbe eosrtdta dpnci acts adiponectin that demonstrated been has It . a (38) HSl n ce,upbihdresults). unpublished Eckel, J and Sell (H (9) nadto,svrlceoie,in- chemokines, several addition, In . oee,i sdfcl oseuaeon speculate to difficult is it However, . . https://doi.org/10.1017/S0029665109990218 (34) slwrin lower is , (34) (53) . IPaddress: hmrnmN expres- mRNA Chemerin . oprsno different of comparison A . .obesus P. (9,34,52) 170.106.33.19 db/db hmtci yoie,oeiyadtp ibts381 diabetes 2 type and obesity cytokines, Chemotactic (49) (51) Accordingly, . nhuman In . mice (9) oai is Eotaxin . single A . , on (27) (54) 29 Sep2021 at12:17:59 . b (32) u is but and ,is upiigy hmrnisl nrae lcs paein uptake glucose increases account. 3T3-adipocytes into itself taken chemerin be Surprisingly, to have organs chemerin-producing poieefc nadipocytes on effect opposite uhhge fnt hnceei tefadeetpotent macrophages exert activated and on itself effects chemerin anti-inflammatory than with CMKLR1 affinity to higher bind much cleavage protease cysteine by merin si atmcohgs lhuhohrclsi adipose secretion in tissue cells cells adipose vascular and other to preadipocytes contribute although adipocytes, as macrophages, such pro- tissue fact been adipokines pro-inflammatory has in of It source is liver. main the or that muscle posed in numbers macrophage iual nrlto otevsea a depot fat visceral par- the between tissue, to correlation adipose relation into good in infiltration ticularly a macrophage for and BMI evidence provided have ei id otoGpoenculdrcpos P1and GPR1 other 2 receptors, Che- receptors G-protein-coupled CCR-like recently. two identified to to been binds binding merin have chemerin-derived by which CMKLR1, explained and than be chemerin can of peptides effect divergent This inflammation and coagulation invol- the cascades of peptide proteases carboxy-terminal serine a by ving agonist of CMKLR1 cleavage a to proteolytic rapidly converted is Prochemerin ensont ecaatrsi fepnigaioetis- adipose expanding of characteristic pro- be sue of to release shown recently increased has been to infiltration inflammation macrophage addition chronic markers, In inflammatory of tissue. state adipose a in with associated is Obesity known. not is of diabetes context 2 the type in and peptides obesity chemerin-derived and receptors hmrn hc a o fnt oCMKLR1 to affinity low pro- a as synthesized dif- has from is completely derived Chemerin which have action. peptides to chemerin, of shown as modes been well ferent have receptors as other that New targets identified chemerin CMKLR1. involve receptor been protein its have and this chemerin of than actions the because actions. autocrine or paracrine and endocrine its hmrnepeso naioye su euae by regulated results). up unpublished is Eckel, adipocytes J in IL-1 and expression Sell skeletal Chemerin (H in resistance cells insulin muscle induces chemerin that strated noaioetsu.I dps iseo bs patients obese of found been tissue have adipose adipocytes apoptotic surrounding infiltration macrophages In of macrophage structures tissue. crown-like to adipose contribute into and hypertrophy might adipocyte as hyperplasia well as signals endocrine and scmaal ihta o te hmknssc as such chemokines other for to RANTES that or binding with that MCP-1 process comparable a only In response, is inflammatory cells. peptides an neighbouring inhibit CMKLR1 on chemerin-derived CMKLR1 carboxy- contrast, the to present domain and CCR-like domain to terminal acti- amino-terminal bind its also directly with can 2 CMKLR1, chemerin however, to cells; vating domain carboxy-terminal its h urn nweg fceei scomplicated is chemerin of knowledge current The , subjectto theCambridgeCore termsofuse,available at ehnsso dps iseiflmainwt a with inflammation tissue adipose of Mechanisms (61) b (55) oee,oeiyi o soitdwt increased with associated not is obesity However, . (33) hs hmrnmyeetdfeetefcsby effects different exert may chemerin Thus, . oeta oefrchemoattractants for role potential abx-emnlppie eie rmche- from derived peptides Carboxy-terminal . (57,58) (54) oeseicly hmrnbnswith binds chemerin specifically, More . lhuhaohrsuyhsrpre the reported has study another although , (59,60) h oeo h oe chemerin novel the of role The . (64) (55) h xrsino several of expression The . n thsbe demon- been has it and (62) lnclstudies Clinical . (63) Paracrine . (56,57) (33) . . https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society 8 .Sl n .Eckel J. and Sell H. 382 rncito atrhpxaidcbefco 1 factor inducible hypoxia factor transcription hypoxia (72) contribute receptor this activation for and attraction state macrophages, ligands macrophage to that newly-recruited chemokine obese possible in it of CCR2 the making as expression in such increased receptors increased with is concomitantly cytokines chemotactic as fedpamcrtclmstress reticulum endoplasmic of cause arpae naioetissue adipose M2-like in more of occurrence macrophages the by accompanied is subjects hl hi bs itrae r hrceie yan by characterized are animals, littermates O lower lean 60% obese com- in approximately is oxygenation their oxygenation tissue while that general mice with it in tissue, parable adipose demonstrated to been relation has In situations. pathological and tae nhmnsbet hthpxaocr nteobese the in occurs hypoxia that state subjects human in strated ytei sarsl ficesdeeg viaiiyor protein in availability resistance increased insulin energy of result increased tissue including a adipose of as obesity, deprivation result glucose even in a as parti- expla- fat occurs synthesis several stress in reticulum are endoplasmic cularly is There why investigation of stress. nations under reticulum currently endoplasmic hypoxia with associated known. yet not is hypoxia rlfrto,agoeei,guoemtbls n the and metabolism matrix cell glucose example, extracellular for angiogenesis, affect, that proliferation, genes various 1 of factor transcription inducible Hypoxia tissues. in ability u hster napyilgclcneti recent in context physiological a in have studies theory enlightening years very this some as put timely, is obesity of not are mechanisms obesity the in understood. yet tissue that adipose emphasized to recruitment be macrophage must it However, ncnrs,terlaeo dpnci sdcesdin decreased is adiponectin stress reticu- endoplasmic of lum of activation release through possibly the hypoxia, contrast, In faioie n h eeomn foeiyadthe and obesity of development the production syndrome increased and metabolic the adipokines underlies hypoxia of mice of tissue eae,a inligptwy o ohfrso stress of forms both for pathways signalling closely be as might stress related, reticulum endoplasmic and hypoxia rncoi adipocytes apoptotic large, of necrotic uptake the for or necessary pro- be a may cytokines, that pro-inflammatory cess to activated addition anti-inflammatory in alternatively secrete cytokines to for able are that markers (M2) the macrophages surface that shown express has latter macrophages tissue-resident adipose of L6 etnadvsua nohla rwhfactor growth endothelial of vascular in release and observed increased same that leptin including the as tissue, IL-6, to cell function adipose leads this secretory expanded adipocytes in of isolated behaviour dysregulation in secretory Hypoxia and type. in changes expression various causes protein hypoxia that shown have pocytes e oei h dpiersos odcesdO decreased to response adaptive the in role key a bst scaatrzdb wthn h macrophage status the M1 inflammatory switching classical by towards characterized phenotype is obesity nte ehns faioetsu inflammation tissue adipose of mechanism Another h td fhpxai dps isei h otx of context the in tissue adipose in hypoxia of study The h euaino te hmtci rtisby proteins chemotactic other of regulation The . (22) https://www.cambridge.org/core (68) ehnsial,hpxalast ciaino the of activation to leads hypoxia Mechanistically, . (73) yoi a enosre nbt physiological both in observed been has Hypoxia . (70) hl C- erto ssihl decreased slightly is secretion MCP-1 while , h ees fRNE sicesdby increased is RANTES of release The . (74) yoi a lobe rpsdt ea be to proposed been also has Hypoxia . . https://doi.org/10.1017/S0029665109990218 (71) (70) yoi tde nioae adi- isolated in studies Hypoxia . utemr,i a endemon- been has it Furthermore, . (65) egtrdcini human in reduction Weight . . IPaddress: 2 rsuei fat in pressure (66) 170.106.33.19 (65) hl diet-induced while (70) Characterization . Furthermore, . a (69) a , on nrae the increases nadipose In . hc has which , 29 Sep2021 at12:17:59 2 avail- (67) (72) . . eg ncmo ahassc satvto fmam- kinase of N-terminal c-Jun activation or as rapamycin such of target pathways malian common in merge .S n .E ohrvee h xsigltrtr and literature existing the reviewed article. both the writing E. gratefully to interest. J. contributed of is and conflict Hurow S. no H. declare Birgit authors of The acknowledged. assistance secretarial HEALTH-F2–2008–201100). The the no. Technical (Collaborative and contract Communities ADAPT, syndrome) and Project European metabolic the the Scientific of key of Commission A prevention of tissue: for (Adipose field target BM0602 Action the (COST) Research in Cooperation fu the fu Nordrhein-Westfalen, Ministerium Landes Bundesministerium des the Forschung by und supported schaft was work This and of obesity treatment the of better for diseases. a pathways pathophysiology obesity-related Finally, to involved lead targeting the future. facilitate might hypoxic of the tissue adipose and in understanding insulin in that inflammation diabetes occurring of biomarkers tissue events prevention 2 new adipose the type understanding define optimizing and in to resistance helpful serve be also may therapeutic and potential new targets chemokine provide and eventually adipokine role could of key release a Analysis play resistance. could insulin 2 that in type state as inflammatory with chronic such also grade and proteins obesity other with diabetes new correlate and of that chemokines chemerin development proteins, the clinical chemo- many patho- tactic for both secretes the tissue and Adipose in of strategies. understanding therapeutic obesity perspectives better of new a for physiology to science led basic and has tissue obser- adipose obesity The expanded diabetes. in infiltrate 2 macrophages inflam- type that relationships obesity, and vation in pathophysiological resistance mass insulin the tissue mation, on adipose opened increased vision has between new function a secretory tissue up adipose on Research , subjectto theCambridgeCore termsofuse,available at .JnsD ilG 19)Nnislndpnetdiabetes Non-insulin-dependent (1997) GV Gill & DB Jones 3. .GrnM,Bl D&Cu L(03 bst n ikof risk and Obesity (2003) ML Cruz & GD Ball MI, Goran 4. .DsrsJ 20)I icrloeiytecueo h meta- the of cause the obesity visceral Is (2006) JP Despres 2. .DnoaP laaA huhr A Chaudhuri A, Aljada P, Dandona 1. elts In mellitus. ye2daee n adoaclrdsaei hlrnand children in disease cardiovascular and adolescents. diabetes Blackwell 2 Oxford: type editors]. Williams, G and Science. Pickup [JC oi syndrome? bolic ewe bst,daee,adinflammation. and diabetes, 111 obesity, interactions on between based perspective comprehensive a syndrome: 1448–1454. , nvivo in lnEdcio Metab Endocrinol Clin J etoko Diabetes of Textbook hs dpknspriiaei low- a in participate adipokines These . Acknowledgements n Med Ann ¨ eudet h UEuropean EU the Gesundheit, r Conclusion References 38 52–63. , n d,p.17.1–17.13 pp. ed., 2nd , tal. et 88 1417–1427. , 20)Metabolic (2005) ¨ Circulation Wissen- r (70) . https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society 2 acloR eea ,Vgei N Viguerie C, Henegar R, Cancello 22. 1 ru M inA,Pdre SB Pedersen AS, Lihn JM, Bruun 21. S Kriwanek HP, Kopp GH, Schernthaner 20. 9 iGeoi B a-oegse ,RsuiN Rasouli A, Yao-Borengasser GB, Gregorio Di 19. T Claudi KT, Lappegard M, Troseid 18. BR Winkelmann MM, Hoffmann E, Simeoni 17. 4 aaao E reiiF oa C Coman F, Ermetici AE, Malavazos 14. 6 imniL aoiG ecliA Mercalli G, Calori L, Piemonti 16. B Thorand J, Baumert C, Herder 13. 5 ue ,Kee W ed M Zeyda FW, Kiefer J, Huber 15. T Kawada HS, Park CS, Kim 12. Monocyte (2005) JM Bruun & B Richelsen T, Christiansen 11. 0 agoiiM(98 hmknsadluoyetraffic. leukocyte and Chemokines (1998) M Baggiolini 10. .AglsJ,LpzSraoJ ledoV Almendro J, Lopez-Soriano JM, Argiles 5. .Bzol ,Blo ,MMla J McMillan K, Bolton K, Bozaoglu Chemokines. (1997) 9. BJ obesity. Rollins in 8. changes tissue Adipose (2005) SW Coppack 7. lipid- of mechanisms Molecular (2005) M Roden & M Krebs 6. incagsi ht dps iseo obdyobese morbidly loss. of weight tissue surgery-induced adipose 2277–2286. white after in expres- subjects gene changes chemoattractant and sion infiltration macrophage of uctnoshmnaioetsu A) mlcto of Implication AT. (AT): the 90 than in tissue visceral resident adipose in macrophages higher human is subcutaneous release protein-1 monocyte-chemoattractant- chemoattractant and obesity. morbid interleukin-18 serum in on protein-1 surgery of bariatric by induced levels loss weight massive of inwt yoieepeso,islnrssac,and resistance, insulin expression, associa- pioglitazone. tissues: cytokine by muscle reduction and with pro- adipose chemoattractant human tion in macrophage genes and tein-1 CD68 of Expression eue lsalvl fteceoie C- n IL-8 syndrome. and metabolic MCP-1 the chemokines 349–355. with the subjects of in levels plasma reduces resistance insulin mellitus. diabetes and 2 gene Type and protein-1 chemoattractant mono- the cyte in polymorphism A-2518G the between Association icanraiisi icrlobesity. car- visceral on in levels adipocytokine abnormalities and diac tissue adipose epicardial of 1984–2002. study, MONICA/ the from 921–929. Augsburg results diabetes: 2 type KORA for factors risk as ouaino lcs-oeatadglucose-intolerant and mortality. 2, cardiovascular glucose-tolerant 26 on receptor a impact in of women: factor-alpha concentration 1 necrosis protein population chemoattracting tumor monocyte and leptin, plasma n Cceoiercpo rfie nvsea n sub- and visceral obesity. human in in Metab altered Endocrinol profiles are tissue receptor adipose cutaneous chemokine CC and 132–134. and subjects obese 30 human parameters. in obesity-related elevated with are associated IL-8 and in MCP-1 loss of weight after reduced subjects. obese and morbid adiposity adipocytes, isolated with in associated produced is protein-1 chemoattractant 392 nue nui eitnei uce ie n vasculature. and liver Metab muscle, Obes in Diabetes resistance insulin induced link a tissue: adipose obesity? and with muscle skeletal between Cross-talk oe dpkn soitdwt bst n metabolic and obesity with associated adipokine syndrome. novel a hmScTrans Soc chem 2282–2289. , 2883–2889. , 1347–1355. , https://www.cambridge.org/core 565–568. , Endocrinology e e Rev Res Med 33 93 . 1049–1052. , https://doi.org/10.1017/S0029665109990218 3215–3221. , 7 n bs(Lond) Obes J Int 621–632. , 148 Diabetes 25 . IPaddress: bsSurg Obes 4687–4694. , tal. et Diabetologia 49–65. , tal. et Blood tal. et lnEdcio Metab Endocrinol Clin J tal. et 20)Cruaiglevels Circulating (2006) 54 tal. et tal. et 170.106.33.19 hmtci yoie,oeiyadtp ibts383 diabetes 2 type and obesity cytokines, Chemotactic tal. et 20)C chemokine CC (2008) tal. et tal. et 2305–2313. , 90 16 20)Chemokines (2006) n Cardiol J Int 909–928. , 20)Ceei is Chemerin (2007) tal. et 29 709–715. , Diabetologia n bs(Lond) Obes J Int 20)Monocyte (2005) 20)Reduction (2005) u er J Heart Eur 47 20)Influence (2006) 146–150. , 20)Exercise (2004) 20)Fasting (2003) ibtsCare Diabetes 1574–1580. , tal. et Diabetes 20)Effect (2006) tal. et tal. et , on 29 Sep2021 at12:17:59 Nature (2005) (2004) (2005) Clin J 121 Bio- 54 25 49 , , , , 0 anJ aa K(05 euaino ooyechemo- monocyte of Regulation (2005) AK Madan & JN Fain 40. 9 kr ,AbriHbrC edrC Herder C, Alberti-Huber T, Skurk 39. M Vulcano JD, Franssen V, Wittamer 33. S Lagarrigue G, Lazennec C, Chavey 32. 8 iteShodrD elH hi M Uhlig H, Sell D, Dietze-Schroeder 38. EA Hanniman TC, McCarthy KB, Goralski 34. 1 edrC cnilrS ahanW Rathmann S, Schneitler C, Herder 31. 7 ehrtC,Rmr A acloR Cancello IA, Romero CC, Gerhardt 37. chemoattractant Monocyte (2003) DJ Loskutoff & P Sartipy 35. 6 elH iteShodrD asrU Kaiser D, Dietze-Schroeder H, Sell 36. 0 otrV aavI&SihU(03 nelui- (IL-6) Interleukin-6 (2003) U Smith & I Nagaev V, Rotter 30. 9 tazosiM zei-tazosaS tpe A Stepien S, Dzienis-Straczkowska M, Straczkowski 29. 8 ru M eesnS ihle 20)Rglto of Regulation (2001) B Richelsen & SB Pedersen JM, Bruun 28. 7 auea R uH yai AM Xydakis H, Wu AR, Vasudevan 27. S Muller-Scholze B, Haastert C, Herder 26. S Shah Q, Chen P, Jiao 25. M Sandqvist A, Hammarstedt G, Murdolo 24. 3 ahmt ,Wd ,Hd A Hida J, Wada I, Hashimoto 23. , subjectto theCambridgeCore termsofuse,available at trcatpoen1(C-)rlaeb xlnso human of explants by tissue. release adipose (MCP-1) visceral 1 protein expression attractant adipokine 2006. and December 12 size Epublication secretion. adipocyte and between ship iad5i naioetsu eie atrta ik obesity links that factor resistance. derived insulin adipose-tissue to an is 5 ligand h ees fislnrssac-nuigfactors. resistance-inducing prevents insulin cells 54 fat of human release on the adiponectin of action cul- Autocrine by secretion leptin and adipocytes. human accumulation tured fat control kines and adipogenesis regulates metabolism. that adipocyte adipokine novel a Chemerin, novel fluids. 198 inflammatory a human chemerin, from by ligand processed cells antigen-presenting of recruitment adolescents. Metab in Endocrinol resistance Clin insulin J and obesity, inflammation, rti noeiyadislnresistance. insulin and USA obesity Sci in 1 protein L8adtmrncoi atrapa vrxrse in overexpressed subjects. factor-alpha, insulin-resistant from 278 necrosis like cells is, fat tumor and tumor human adipocytes and 3T3-L1 and in IL-8 mass resistance insulin fat induces to related and 4602–4606. increased system. factor-alpha are subjects necrosis concentrations obese interleukin-8 in Plasma (2002) rs-akbtenaioetsu n kltlmuscle. skeletal and negative tissue the in adipose player Endocrinology potential between a cross-talk is protein-1 chemotactic nelui rdcinadgn xrsini ua adi- human in vitro. expression in gene tissue and pose production 8 interleukin lcs oeac n ye2daee:rslsfo the Augsburg obesity. of from and Region results the S4). diabetes: (KORA in 2 S4 Research Survey type Health and impaired Cooperative with tolerance concentrations glucose chemokine systemic of ciation 799–811. uaino ooyeceoatcfcosi adipocytes: NH2-term- in c-Jun pathways. and factors kinase factor-kappaB inal chemotactic nuclear of monocyte involvement of gulation insulin. interstitial by subcutaneous Metab expression of Endocrinol gene Clin of in characterization J regulation and tissue: protein-1 concentration adipose chemoattractant abdominal Monocyte inflam- chronic subjects. and overweight in protein-4 mation chemoattractant monocyte 2003–2011. , 977–985. , 45777–45784. , 100 7265–7270. , lnEdcio Metab Endocrinol Clin J 147 lnEdcio Metab Endocrinol Clin J 2458–2467. , lnEdcio Metab Endocrinol Clin J elMetab Cell Diabetes ilChem Biol J n bs(Lond) Obes J Int Diabetes o elEndocrinol Cell Mol tal. et 92 92 4569–4574. , 2688–2695. , lnEdcio Metab Endocrinol Clin J tal. et 58 20)Oeiyrltdupre- Obesity-related (2009) bst Sle Spring) (Silver Obesity 9 54 104–115. , 339–349. , up.2 S11–S17. 2, Suppl. , 282 tal. et 20)Eeae serum Elevated (2006) tal. et tal. et 91 tal. et tal. et tal. et 28175–28188. , 256–261. , tal. et tal. et 29 20)Low-grade (2007) 20)Monocyte (2006) 20)Relation- (2007) 92 rcNt Acad Natl Proc 1299–1307. , 86 20)Chemo- (2001) 20)Specific (2003) 20)Eotaxin (2006) tal. et 175 1023–1033; , tal. et tal. et 20)Asso- (2005) 1267–1273. , 20)CXC (2009) ilChem Biol J x Med Exp J 81–92. , Diabetes (2005) (2007) (2007) tal. et 87 14 , , https://www.cambridge.org/core/terms Downloaded from Proceedings of the Nutrition Society 2 o G ogS,Co KC Choi SH, Song SG, Roh 52. 3 ae A haaT uiaL Zuniga T, Ohyama BA, Zabel 53. C Thamer A, Fritsche O, Adiponectin: Tschritter (2005) 50. B Richelsen & SB Pedersen AS, Lihn 49. HC Kadouh HB, IglayReger SJ, Yang 48. 7 auaY uiooM uaaaT Murayama M, Sugimoto Y, Tamura 47. 8 .Sl n .Eckel J. and Sell H. 384 4 aaah ,TkhsiY aaah K Takahashi Y, Takahashi M, Takahashi 54. B Haastert H, Hauner C, Herder 51. 6 esegS,Hne ,HbrR Huber D, Hunter SP, Weisberg 46. Y Tamori S, Tateya H, Kanda 42. 6 itmrV rgieF obrctP Robberecht F, Gregoire V, Wittamer 56. G Sommer S, Weise S, Kralisch 55. 5 hnA uikS hn C Zhang S, Mumick A, Chen 45. R Suzuki K, Tobe N, Kamei 44. JK Howard H, Shi KE, Inouye 43. 1 asae ,KenJ rlshS Kralisch J, Klein M, Fasshauer 41. 7 ahJ,Hr ,Rs A Russ R, Hart JL, Cash 57. 8 ae A aa ,Zng L Zuniga S, Nakae BA, Zabel 58. dpkn htmdltsaioeei i t w receptor. own Commun its Res via Biophys adipogenesis Biochem modulates that adipokine cin euainadascaint nui sensitivity. insulin to and Rev association steatosis and regulation hepatic action, of model and (C-C mouse hyperglycaemia 2/chemokine a attenuates lipoatrophy. ligand in pathway motif) 2 inflammation (C-C receptor chemokine motif) the of 2195–2201. eino usugSre KR S4). the (KORA in 4 Research Survey 29 Health Augsburg Cooperative of same the the Region from of sides results two coin?: state: proinflammatory and nectinemia eetr1epeso ymcohgsi io euainby regulation ligands. vivo: TLR in and macrophages TGF-beta by expression 1 receptor both metabolism. lipid of and sensitivity glucose insulin predict concentrations adiponectin taoi nd/bmice. hepatic db/db and in resistance insulin steatosis ameliorates CCR2 of Inhibition high-fat of effects metabolic feeding. and inflammatory modulates bt nue h oe dpkn hmrni adipocytes in chemerin adipokine novel vitro. in the induces 1beta tmltdguoeutk n33L adipocytes. 3T3-L1 in 582 insulin- uptake potentiates glucose and stimulated signaling insulin enhances Chemerin fmnct hmatatn rti- n t maton impact its and protein-1 chemoattractant obesity. monocyte of resistance. 281 insulin and causes recruitment tissues adipose macrophage in protein-1 chemoattractant monocyte obesity-associated limit tissue. not adipose into 2242–2250. does macrophages 2 of infiltration ligand chemokine CC obesity. in 1494–1505. insulin steatosis tissue, hepatic adipose and into resistance, infiltration macrophage to tributes adipocytes. 3T3-L1 Commun Res in Biophys growth interleukin-6 by and stimulated is hormone expression 1 protein chemoattractant -emnlnnppieo aueceei ciae the activates potency. chemerin nanomolar 279 low mature with receptor of chemerin nonapeptide C-terminal xrse rhnrcpo CL id hmrnadis and chemerin binds CCRL2 receptor orphan expressed ChemR23. through Med Exp inflammation J suppress peptides derived https://www.cambridge.org/core 1626–1631. , 573–578. , 26602–26614. , 9956–9962. , 6 13–21. , bsRes Obes lnInvest Clin J eu Pept Regul 205 Diabetologia 767–775. , . https://doi.org/10.1017/S0029665109990218 13 154 1311–1320. , 116 317 102–106. , reislrTrm acBiol Vasc Thromb Arterioscler 115–124. , . IPaddress: 598–604. , 52 tal. et x Hematol Exp 972–981. , tal. et tal. et Diabetes 362 tal. et tal. et 20)Snhtcchemerin- Synthetic (2008) tal. et tal. et tal. et tal. et tal. et 20)Ceei new a – Chemerin (2007) 20)Oeepeso of Overexpression (2006) 1013–1018. , 170.106.33.19 tal. et 20)Chemokine-like (2006) tal. et 20)De induction Diet (2005) tal. et tal. et 52 20)MP1con- MCP-1 (2006) 20)Asneof Absence (2007) 20)Hypoadipo- (2006) 20)Interleukin- (2009) 20)Ms cell- Mast (2008) 34 tal. et 239–243. , lnInvest Clin J 20)Monocyte (2004) 20)Inhibition (2009) 1106–1114. , 20)Plasma (2003) tal. et ibtsCare Diabetes 20)CCR2 (2006) , on tal. et ilChem Biol J Diabetes ilChem Biol J 20)The (2004) 29 Sep2021 at12:17:59 ESLett FEBS Biochem (2008) (2008) Obes 116 28 56 , , , 6 edrC anrH ep K Kempf H, Hauner C, Herder 76. 6 lmn ,Vgei ,Pio C Poitou N, Viguerie K, Clement 66. 3 ed ,Fre ,TdrcJ Todoric D, Farmer M, Zeyda 63. 5 aaiR aatriuK gtnN Ogston K, Karastergiou R, Madani the 75. stress: Adipocyte (2007) GS Hotamisligil & MF Gregor 74. K Kempf I, Mack T, Skurk 73. therapy. cancer for HIF-1 Targeting (2003) GL Semenza 71. K Oshima A, Fukuhara N, Hosogai 70. JL Bodzin SM, Deyoung CN, Lumeng 65. V Parisani G, Barbatelli I, Murano 64. 8 SWo,FPe F Wood, IS 68. induces Obesity (2007) AR Saltiel & JL Bodzin CN, Lumeng 67. 2 anJ 20)Rlaeo neluisadohrinflamma- other and interleukins of Release (2006) JN Fain 62. AJ Hoogewerf CA, Power AE, Proudfoot 60. 2 agB odI ryunP(07 yrglto of Dysregulation (2007) P Trayhurn & IS Wood B, Wang 72. 9 eJ a ,YnJ Yin Z, Gao J, Ye 69. 9 hn oln J(95 oiatngtv inhibitor negative dominant A (1995) BJ Rollins & Y Zhang 59. 1 esegS,MCn ,DsiM Desai D, McCann SP, Weisberg 61. , subjectto theCambridgeCore termsofuse,available at nuil rti 0(P1/XL0 nhmnadipocytes. interferon-gamma- (Lond) human Obes in of J (IP-10/CXCL10) Int secretion 10 protein and inducible expression regulated produc- phenotype mediator pro-inflammatory anti-inflammatory tion. excessive an of of capable but are macrophages tissue ees yhmnaioetsu nvv n vdnefor evidence and vivo in 296 differences. tissue specific adipose depot human by release 1905–1914. disease. metabolic and reticulum endoplasmic 479–492. macrophages tissue adipose obesity. diet-induced of during recruited properties inflammatory 1562–1568. hntpcsic naioetsu arpaepolariza- macrophage tissue adipose in tion. switch phenotypic a tissue adipose subjects. white obese in of genes inflammation-related regulates oyctknsb ua dps isei nacdin enhanced cells. is nonfat the tissue to adipose due 74 primarily human and by obesity cytokines tory erto fRNE CL)i ua dpctsin adipocytes human in hypoxia. and Res (CCL5) stimuli immunological RANTES to response of secretion adipocytes. human adipo- in inflammation-related hypoxia of by secretion kines and expression the adipocytokine Cancer on Rev impact its and obesity dysregulation. in hypoxia tissue mice. obese dietary Metab in and Endocrinol reduction ob/ob of adiponectin tissue and adipose inflammation chronic for factor mice. obese genetically of in depots prevalent fat are structures, visceral crown-like as detected adipocytes, niae htmnct hmatatn rti functions 1 dimer. protein a chemoattractant as monocyte that indicates soitdwt arpaeacmlto naioetissue. adipose Invest in Clin accumulation J macrophage antagonist. with associated potent a produces Chem methionine retention Biol the J initiating by the RANTES human of recombinant of Extension yoi n dps isedsucini obesity. in dysfunction Soc tissue adipose and hypoxia eurdfrotmlidcino g-eitdpassive IgE-mediated of induction anaphylaxis. optimal cutaneous for required 443–477. , E1262–E1268. , 41 68 n bs(Lond) Obes J Int lnInvest Clin J 183–189. , I h Press). the (In o elBiol Cell Mol 3 271 112 721–732. , ´ Diabetes e eHrda Wang B Heredia, de rez 2599–2603. , 1796–1808. , AE J FASEB 31 117 293 tal. et 403–410. , 175–184. , E1118–E1128. , x Med Exp J 31 56 1420–1428. , 15 20)Hpxai oeta risk potential a is Hypoxia (2007) 901–911. , mJPyilEdcio Metab Endocrinol Physiol J Am 18 4851–4855. , tal. et 1657–1669. , tal. et tal. et tal. et 205 tal. et 20)Cntttv and Constitutive (2007) 20)Epeso and Expression (2009) 20)Hmnadipose Human (2007) Diabetes tal. et tal. et 2207–2220. , tal. et tal. et tal. et 20)Wih loss Weight (2004) flgr Arch Pflugers 20)Oeiyis Obesity (2003) 20)Increased (2007) 20)Adipose (2007) 20)Cellular (2009) ii Res Lipid J ii Res Lipid J 20)Rantes (2009) tal. et 20)Dead (2008) mJPhysiol J Am 56 ia Horm Vitam omMetab Horm 16–23. , rcNutr Proc (1996) 455 Nat 49 48 , , ,