Abstract
Leptin, as one of the most important cytokines within the circulation, has been confirmed to play a vital role in the hypothalamus of the central nervous system (CNS), which could modulate energy homeostasis by suppressing food intake. Furthermore, leptin could also influence cell metabolism by acting directly on the leptin receptor, which is a relatively small peptide and is mainly produced and released by fat tissue in mammals. On the other hand, the excessive extracellular matrix (ECM) could induce damage in normal tissues or organ structures, which might further induce fibrotic development in multiple tissues or organs, including the liver, heart, and kidneys. Notably, the sustainable development of fibrosis promotes the structural lesion and functional decline of different organs, which subsequently threatens human health and poses serious risks to human life. Emerging evidence has shown that leptin plays an important role in the fibrotic progression within multiple tissues and organs in mammals and has an alleviating effect on fibrosis. Concerning this notion, it has been proposed that leptin could be identified as a vital therapeutic strategy for fibrotic progression in clinical practice. Consequently, this review summarized the potential mechanisms of leptin in modulating fibrotic development in diverse tissues and organs to provide a theoretical basis for treating fibrotic-related diseases. In addition, the potential mechanisms whereby leptin affects the development of fibrosis were also summarized in the current review.
[http://dx.doi.org/10.1159/000452908] [PMID: 28245454]
[http://dx.doi.org/10.1556/2060.2020.00038] [PMID: 33355539]
[http://dx.doi.org/10.3389/fphar.2021.705252] [PMID: 34526895]
[http://dx.doi.org/10.1016/j.ejphar.2021.174462] [PMID: 34536366]
[http://dx.doi.org/10.1016/j.matbio.2018.01.013] [PMID: 29371055]
[http://dx.doi.org/10.1002/adbi.201900286] [PMID: 32529801]
[http://dx.doi.org/10.1016/j.metabol.2014.09.010] [PMID: 25305050]
[http://dx.doi.org/10.1210/er.2012-1053] [PMID: 23475416]
[http://dx.doi.org/10.2174/156652409787847191] [PMID: 19355912]
[http://dx.doi.org/10.1007/s10528-016-9751-z] [PMID: 27313173]
[http://dx.doi.org/10.3389/fendo.2017.00030] [PMID: 28270795]
[http://dx.doi.org/10.1016/j.taap.2019.114871] [PMID: 31881177]
[http://dx.doi.org/10.1016/j.tem.2010.08.002] [PMID: 20846876]
[http://dx.doi.org/10.1074/jbc.RA119.011881] [PMID: 32047110]
[http://dx.doi.org/10.1159/000095328] [PMID: 16929141]
[http://dx.doi.org/10.1126/scisignal.abm4425] [PMID: 34546792]
[http://dx.doi.org/10.1172/JCI24282] [PMID: 15690074]
[http://dx.doi.org/10.1038/nrendo.2016.222] [PMID: 28232667]
[http://dx.doi.org/10.1007/s00210-019-01703-5] [PMID: 31367862]
[http://dx.doi.org/10.1038/s41598-017-06997-0] [PMID: 28747790]
[http://dx.doi.org/10.1016/j.tem.2015.01.002] [PMID: 25656826]
[http://dx.doi.org/10.1016/j.bbadis.2015.10.028] [PMID: 26529285]
[http://dx.doi.org/10.3390/biom11010073] [PMID: 33430288]
[http://dx.doi.org/10.1016/j.taap.2017.12.007] [PMID: 29248466]
[http://dx.doi.org/10.1016/j.yexcr.2018.03.015] [PMID: 29548749]
[http://dx.doi.org/10.1016/j.biocel.2012.12.019] [PMID: 23295202]
[http://dx.doi.org/10.3748/wjg.v11.i31.4822] [PMID: 16097051]
[http://dx.doi.org/10.1046/j.1365-2893.2003.00483.x] [PMID: 14738564]
[http://dx.doi.org/10.1042/CS20201004] [PMID: 32857135]
[http://dx.doi.org/10.1053/j.gastro.2009.04.011] [PMID: 19375424]
[http://dx.doi.org/10.1016/S0024-3205(03)00653-2] [PMID: 12954457]
[http://dx.doi.org/10.1038/s41401-021-00666-9] [PMID: 33875797]
[http://dx.doi.org/10.1016/j.physbeh.2017.03.002] [PMID: 28267584]
[http://dx.doi.org/10.1007/s00125-016-3906-7] [PMID: 26983921]
[http://dx.doi.org/10.1016/j.metabol.2014.10.015] [PMID: 25497342]
[http://dx.doi.org/10.1002/hep.22584] [PMID: 19065677]
[http://dx.doi.org/10.3390/genes10030184] [PMID: 30818874]
[http://dx.doi.org/10.1007/s12072-021-10210-w] [PMID: 34014450]
[http://dx.doi.org/10.3389/fphys.2021.708656] [PMID: 34421650]
[http://dx.doi.org/10.1016/j.mvr.2010.05.006] [PMID: 20510252]
[http://dx.doi.org/10.3390/jcm10143104] [PMID: 34300270]
[http://dx.doi.org/10.1160/TH13-01-0073] [PMID: 23595655]
[http://dx.doi.org/10.1016/j.trsl.2014.05.001] [PMID: 24880146]
[http://dx.doi.org/10.1515/hmbci-2013-0060] [PMID: 25389996]
[http://dx.doi.org/10.1016/j.hrthm.2018.06.025] [PMID: 29908372]
[http://dx.doi.org/10.1152/ajpgi.00426.2010] [PMID: 21350183]
[http://dx.doi.org/10.2337/db16-0012] [PMID: 27625023]
[http://dx.doi.org/10.1016/j.cmet.2017.12.005] [PMID: 29320702]
[http://dx.doi.org/10.7150/thno.62820] [PMID: 34522205]
[http://dx.doi.org/10.1038/s41598-017-02848-0] [PMID: 28584304]
[http://dx.doi.org/10.3390/ijms20174266] [PMID: 31480394]
[http://dx.doi.org/10.7150/ijms.21881] [PMID: 29559840]
[http://dx.doi.org/10.1210/jc.2015-4125] [PMID: 26871994]
[http://dx.doi.org/10.1172/JCI60323] [PMID: 22850886]
[http://dx.doi.org/10.1016/S0140-6736(11)60052-4] [PMID: 21719092]
[http://dx.doi.org/10.3389/fimmu.2021.661761] [PMID: 34122421]
[http://dx.doi.org/10.1016/j.imbio.2020.151997] [PMID: 32962817]
[http://dx.doi.org/10.1155/2016/6940480] [PMID: 27642238]
[http://dx.doi.org/10.1016/j.cmet.2015.03.001] [PMID: 25863246]
[http://dx.doi.org/10.1016/j.cmet.2015.05.020] [PMID: 26094890]
[http://dx.doi.org/10.3390/ijms20051078] [PMID: 30832310]
[http://dx.doi.org/10.1016/j.bbrc.2018.03.039] [PMID: 29524411]
[http://dx.doi.org/10.1038/gt.2014.13] [PMID: 24572787]
[PMID: 34109754]
[http://dx.doi.org/10.4103/1673-5374.324861] [PMID: 34558529]
[http://dx.doi.org/10.1002/oby.21565] [PMID: 27312141]
[http://dx.doi.org/10.1038/287795a0] [PMID: 6776413]
[http://dx.doi.org/10.1089/scd.2021.0112] [PMID: 34428952]
[http://dx.doi.org/10.1161/JAHA.121.021369] [PMID: 34482701]
[http://dx.doi.org/10.1152/ajpendo.00174.2019] [PMID: 32154744]
[http://dx.doi.org/10.1101/gad.1693608] [PMID: 18794343]
[http://dx.doi.org/10.1016/j.cmet.2013.06.016] [PMID: 23954640]
[http://dx.doi.org/10.1038/nrm3598] [PMID: 23719536]
[http://dx.doi.org/10.1097/SHK.0000000000000836] [PMID: 28125530]
[http://dx.doi.org/10.1016/j.cmet.2005.11.012] [PMID: 16399502]
[http://dx.doi.org/10.1111/1744-7917.12164] [PMID: 25154865]
[http://dx.doi.org/10.1016/bs.ctdb.2016.01.007] [PMID: 26970635]
[http://dx.doi.org/10.1016/j.mce.2021.111417] [PMID: 34339826]