title: Leptin's regulation of obesity-induced cardiac extracellular matrix remodeling.
abstract: Obesity-induced remodeling of cardiac extracellular matrix (ECM) leads to myocardial fibrosis and ultimately diastolic dysfunction. Leptin, an adipocyte hormone, is emerging as a novel mechanistic link between obesity and heart diseases. Despite the known essential role of leptin in hepatic and renal fibrosis, the in vivo effects of leptin on cardiac ECM remodeling remain unclear. Our objective was to define the role of leptin as a key mediator of pro-fibrogenic responses in the heart. In vitro administration of leptin to primary cardiofibroblasts resulted in significant stimulation of pro-collagen Iα                         (                            1                         ) and a decrease in pro-matrix metalloproteinase (MMP)-8, -9 and -13 gene expressions at 24 h. To study the in vivo pro-fibrotic effect, leptin was administrated to C57BL/6 and leptin-deficient ob/ob mice for 8 weeks. With exogenous leptin ob/ob mice displayed passive diastolic filling dysfunction, coincided with significant increase in myocardial collagen compared with ob/ob controls. We also observed a marked stimulation of pro-collagen IIIα                         (                            1                         ) and suppression of pro-MMP-8, TIMP-1 and -3 gene expressions in leptin-treated ob/ob mice. Our findings suggest pro-fibrotic effects of leptin in the heart, primarily through the predominance of collagen synthesis over degradation.
authors: Sarver Heart Center, College of Medicine, The University of Arizona, Tucson, USA.
authors: Sherma
authors: S
authors: Zibadi
authors: Felina
authors: F
authors: Cordova
authors: Elise H
authors: EH
authors: Slack
authors: Ronald R
authors: RR
authors: Watson
authors: Douglas F
authors: DF
authors: Larson
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D004452:Echocardiography; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020738:Leptin / Q000172:deficiency / Q000494:pharmacology*; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D020738:Leptin; D012333:RNA, Messenger; D019714:Tissue Inhibitor of Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted