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Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice.

Publication ,  Journal Article
Barouch, LA; Berkowitz, DE; Harrison, RW; O'Donnell, CP; Hare, JM
Published in: Circulation
August 12, 2003

BACKGROUND: Whether left ventricular hypertrophy (LVH) in obesity results from increased hemodynamic load or altered neurohormonal signaling remains controversial. Dysregulation of leptin, a neurohormone essential to energy homeostasis, is implicated in the pathogenesis of obesity. Because leptin has cardiovascular bioactivity, we hypothesized that disruption of leptin signaling mediates the development of obesity-associated LVH. METHODS AND RESULTS: We measured left ventricular (LV) wall thickness and LV mass with echocardiography in mice lacking leptin (ob/ob, n=15) or functional receptor (db/db, n=10) and controls at 2, 4, and 6 months of age. None of the mice had LVH at 2 months. Progressive obesity developed in ob/ob and db/db mice. At 6 months, LVH occurred in ob/ob and db/db compared with controls. We observed corresponding myocyte hypertrophy by light microscopy. To separate the direct contribution of leptin deficiency from mechanical effects of obesity, we induced weight loss in 6- to 8-month-old ob/ob mice either by leptin infusion or caloric restriction. Mice in both groups lost similar weight compared with placebo-treated controls. Leptin infusion completely reversed the increase in wall thickness with partial resolution of myocyte hypertrophy, whereas calorie-restricted mice had no decrease in wall thickness and a lesser change in myocyte size. CONCLUSIONS: Together these data show that the effect of leptin on LV remodeling is not attributable to weight loss alone, indicating that leptin has antihypertrophic effects on the heart, either directly or through a leptin-regulated neurohumoral pathway. Disruption of leptin signaling may represent a novel mechanism in LVH and related cardiovascular disorders.

Duke Scholars

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

August 12, 2003

Volume

108

Issue

6

Start / End Page

754 / 759

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Signal Transduction
  • Receptors, Leptin
  • Receptors, Cell Surface
  • Organ Size
  • Obesity
  • Myocytes, Cardiac
  • Myocardium
  • Mice, Mutant Strains
  • Mice, Inbred C57BL
 

Citation

APA
Chicago
ICMJE
MLA
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Barouch, L. A., Berkowitz, D. E., Harrison, R. W., O’Donnell, C. P., & Hare, J. M. (2003). Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation, 108(6), 754–759. https://doi.org/10.1161/01.CIR.0000083716.82622.FD
Barouch, Lili A., Dan E. Berkowitz, Robert W. Harrison, Christopher P. O’Donnell, and Joshua M. Hare. “Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice.Circulation 108, no. 6 (August 12, 2003): 754–59. https://doi.org/10.1161/01.CIR.0000083716.82622.FD.
Barouch LA, Berkowitz DE, Harrison RW, O’Donnell CP, Hare JM. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation. 2003 Aug 12;108(6):754–9.
Barouch, Lili A., et al. “Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice.Circulation, vol. 108, no. 6, Aug. 2003, pp. 754–59. Pubmed, doi:10.1161/01.CIR.0000083716.82622.FD.
Barouch LA, Berkowitz DE, Harrison RW, O’Donnell CP, Hare JM. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation. 2003 Aug 12;108(6):754–759.

Published In

Circulation

DOI

EISSN

1524-4539

Publication Date

August 12, 2003

Volume

108

Issue

6

Start / End Page

754 / 759

Location

United States

Related Subject Headings

  • Ventricular Remodeling
  • Signal Transduction
  • Receptors, Leptin
  • Receptors, Cell Surface
  • Organ Size
  • Obesity
  • Myocytes, Cardiac
  • Myocardium
  • Mice, Mutant Strains
  • Mice, Inbred C57BL