Leptin's regulation of obesity-induced cardiac extracellular matrix remodeling

Sherma Zibadi, Felina Cordova, Elise H. Slack, Ronald R Watson, Douglas F Larson

Research output: Contribution to journalArticle

36 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)325-333
Number of pages9
JournalCardiovascular Toxicology
Volume11
Issue number4
DOIs
StatePublished - Dec 2011

Fingerprint

Leptin
Extracellular Matrix
Obesity
Collagen
Matrix Metalloproteinase 8
Gene expression
Fibrosis
Tissue Inhibitor of Metalloproteinase-3
Gene Expression
Tissue Inhibitor of Metalloproteinase-1
Adipocytes
Heart Diseases
Hormones
Kidney
Degradation
Liver

Keywords

  • Collagen
  • Heart
  • Leptin
  • Obesity

ASJC Scopus subject areas

  • Toxicology
  • Cardiology and Cardiovascular Medicine
  • Molecular Biology

Cite this

Leptin's regulation of obesity-induced cardiac extracellular matrix remodeling. / Zibadi, Sherma; Cordova, Felina; Slack, Elise H.; Watson, Ronald R; Larson, Douglas F.

In: Cardiovascular Toxicology, Vol. 11, No. 4, 12.2011, p. 325-333.

Research output: Contribution to journalArticle

Zibadi, Sherma ; Cordova, Felina ; Slack, Elise H. ; Watson, Ronald R ; Larson, Douglas F. / Leptin's regulation of obesity-induced cardiac extracellular matrix remodeling. In: Cardiovascular Toxicology. 2011 ; Vol. 11, No. 4. pp. 325-333.
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