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Disruption of Leptin Signaling Contributes to Cardiac Hypertrophy Independently of Body Weight in Mice
Open accessAbstract
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.
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“For example, while some groups have reported cardiac hypertrophy in hearts of young ob/ob mice (30, 34, 227), others have only observed this phenotype in older animals (23, 24).”
From Cardiac remodeling in obesity (2008) · cites this paper as [23]
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“Similarly, cardiac hypertrophy has been reported in old but not in young db/db mice (23, 24).”
From Cardiac remodeling in obesity (2008) · cites this paper as [23]
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“One report concluded that leptin mediates antihypertrophic effects since infusion of leptin to ob/ob mice, which exhibit LVH, decreased LV wall thickness (23).”
From Cardiac remodeling in obesity (2008) · cites this paper as [23]
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Metadata
- Authors
- Barouch, L. A., Berkowitz, D. E., Harrison, R. W., O’Donnell, C. P., & Hare, J. M.
- Affiliations
- Johns Hopkins University (US)
- From the Department of Medicine, Divisions of Cardiology (L.A.B., R.W.H., J.M.H.) and Pulmonary Medicine (C.P.O.) and the Department of Anesthesia and Critical Care Medicine (D.E.B.), Johns Hopkins Medical Institutions, Baltimore, Md.
- Venue
- Circulation
- Published
- 2003-08-12
- Volume
- 108
- Issue
- 6
- Pages
- 754-759
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2119801354
- Cited by
- 341
- References
- 36
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 11 · 2023: 9 · 2022: 17 · 2021: 11 · 2020: 13 · 2019: 14 · 2018: 8 · 2017: 20 · 2016: 8 · 2015: 15 · 2014: 15 · 2013: 26 · 2012: 15
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute (K08HL003238, R01HL065455)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- leptin signaling, cardiac hypertrophy, left ventricular hypertrophy, obesity, leptin receptor, ob/ob mice, db/db mice, myocyte hypertrophy, cardiac remodeling, caloric restriction, weight loss, hemodynamic load
- MeSH terms
- Animals, Body Weight, Disease Models, Animal, Cardiomegaly, Heart Ventricles, Hemodynamics, Homozygote, Mice, Inbred C57BL, Mice, Mutant Strains, Myocardium, Obesity, Organ Size, Receptors, Cell Surface, Signal Transduction, Disease Progression, Ventricular Remodeling, Leptin, Myocytes, Cardiac, Mice, Receptors, Leptin
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