Impact of Leptin-Mediated Sympatho-Activation on Cardiovascular Function in Obese Mice
Open accessAbstract
Although the anorexic effects of leptin are lost in obesity, leptin-mediated sympatho-activation is preserved. The cardiovascular consequences of leptin-mediated sympatho-activation in obesity are poorly understood. We tested the hypothesis that 32 weeks of high-fat diet (HFD) induces metabolic leptin resistance but preserves leptin-mediated sympatho-activation of the cardiovascular system. HFD in mice significantly increased body weight and plasma leptin concentrations but significantly reduced the anorexic effects of leptin. HFD increased heart rate, stroke volume, cardiac output, and plasma aldosterone levels but not blood pressure. As reflected by the contractile response to phenylephrine measured both in vivo and ex vivo, vascular adrenergic reactivity was reduced by HFD, suggesting that reductions in sympathetic tone to the periphery vasculature may mitigate sympatho-activation of the heart and the renin-angiotensin-aldosterone system. Tachyphylaxis was partially restored by symptho-inhibition and not present in ob/ob and db/db mice, despite obesity, arguing for a sympatho-mediated and leptin-specific mechanism. Although infusion of leptin in HFD mice had no effect on heart rate or blood pressure, it further increased aldosterone levels and further reduced vascular adrenergic tone in the absence of weight loss, indicating persistent leptin-mediated stimulation of the cardiovascular system in obesity. In conclusion, these data indicate that, despite metabolic leptin resistance, leptin-mediated stimulation of the heart, the vasculature, and aldosterone production persists in obesity. Blood pressure effects in response to leptin may be limited by a tachyphylactic response in the circulation, suggesting that failure of adrenergic desensitization may be a requisite step for hypertension in the context of obesity.
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Multiple mechanisms, including sympathetic overdrive, inflammatory mediators, excessive reactive oxygen species production, and decreased nitric oxide bioactivity, may contribute to the deleterious effects of obesity on the vasculature.
“Multiple other mechanisms including sympathetic overdrive, inflammatory mediators, excessive reactive oxygen species production, decreased NO bioactivity may contribute to the deleterious effects of obesity on the vasculature (70;71;74;75).”
From Obesity-Associated Hypertension: Recent Progress in Deciphering the Pathogenesis (2014) · cites this paper as [74]
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Self-citation
- Authors
- Belin de Chantemèle, E. J., Mintz, J. D., Rainey, W. E., & Stepp, D. W.
- Affiliations
- From the Vascular Biology Center (E.J.B.d.C., J.D.M., D.W.S.), Department of Physiology (E.J.B.d.C., W.E.R., D.W.S.), Georgia Health Sciences University, Augusta, GA.
- Venue
- Hypertension
- Published
- 2011-08
- Volume
- 58
- Issue
- 2
- Pages
- 271-279
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC3141100
- OpenAlex
- W2097954820
- Cited by
- 103
- References
- 43
- Citations by year
- 2026: 6 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 8 · 2021: 3 · 2020: 7 · 2019: 9 · 2018: 7 · 2017: 11 · 2016: 5 · 2015: 7 · 2014: 10 · 2013: 7 · 2012: 8
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL092446)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Surgery › Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Keywords
- leptin, obesity, high-fat diet, cardiovascular function, heart rate, stroke volume, cardiac output, aldosterone, renin-angiotensin-aldosterone system, phenylephrine response, tachyphylaxis, ob/ob mice, db/db mice, leptin resistance
- MeSH terms
- Aldosterone, Animals, Blood Pressure, Cardiovascular System, Dietary Fats, Heart Rate, Hypertension, Male, Obesity, Renin-Angiotensin System, Sympathetic Nervous System, Leptin, Mice
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