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Exposure to a High-Fat Diet Alters Leptin Sensitivity and Elevates Renal Sympathetic Nerve Activity and Arterial Pressure in Rabbits
Open accessAbstract
The activation of the sympathetic nervous system through the central actions of the adipokine leptin has been suggested as a major mechanism by which obesity contributes to the development of hypertension. However, direct evidence for elevated sympathetic activity in obesity has been limited to muscle. The present study examined the renal sympathetic nerve activity and cardiovascular effects of a high-fat diet (HFD), as well as the changes in the sensitivity to intracerebroventricular leptin. New Zealand white rabbits fed a 13.5% HFD for 4 weeks showed modest weight gain but a 2- to 3-fold greater accumulation of visceral fat compared with control rabbits. Mean arterial pressure, heart rate, and plasma norepinephrine concentration increased by 8%, 26%, and 87%, respectively ( P <0.05), after 3 weeks of HFD. Renal sympathetic nerve activity was 48% higher ( P <0.05) in HFD compared with control diet rabbits and was correlated to plasma leptin ( r =0.87; P <0.01). Intracerebroventricular leptin administration (5 to 100 μg) increased mean arterial pressure similarly in both groups, but renal sympathetic nerve activity increased more in HFD-fed rabbits. By contrast, intracerebroventricular leptin produced less neurons expressing c-Fos in HFD compared with control rabbits in regions important for appetite and sympathetic actions of leptin (arcuate: −54%, paraventricular: −69%, and dorsomedial hypothalamus: −65%). These results suggest that visceral fat accumulation through consumption of a HFD leads to marked sympathetic activation, which is related to increased responsiveness to central sympathoexcitatory effects of leptin. The paradoxical reduction in hypothalamic neuronal activation by leptin suggests a marked “selective leptin resistance” in these animals.
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“The relationship among insulin, leptin, and MAP appears more complex than we have reported previously, 9 because the rising trend of MAP follows that of insulin and leptin during the onset of obesity but does not appear to hold after the withdrawal of HFD, where plasma leptin and insulin concentrations fall rapidly but MAP and RSNA remain high.”
From Rapid Onset of Renal Sympathetic Nerve Activation in Rabbits Fed a High-Fat Diet (2012) · cites this paper as [9]
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Region-Specific Leptin Resistance within the Hypothalamus of Diet-Induced Obese Mice
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Chronic Leptin Infusion Increases Arterial Pressure
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Sympathetic Activation in Obese Normotensive Subjects
Grassi, G., Seravalle, G., Cattaneo, B. M., Bolla, G. B., Lanfranchi, A., Colombo, M., Giannattasio, C., Brunani, A., Cavagnini, F., & Mancia, G. (1995) · Hypertension · doi:10.1161/01.hyp.25.4.560 · Cited by 614
Diet-Induced Obesity Causes Severe but Reversible Leptin Resistance in Arcuate Melanocortin Neurons
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Leptin Activates Neurons in Ventrobasal Hypothalamus and Brainstem
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Odermatt, A. (2011) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00068.2011 · Cited by 262
The Role of Aldosterone in Obesity-Related Hypertension
Kawarazaki, W., & Fujita, T. (2016) · American Journal of Hypertension · doi:10.1093/ajh/hpw003 · Cited by 170
Selective leptin resistance revisited
Mark, A. L. (2013) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00180.2013 · Cited by 162
Obesity-related hypertension: possible pathophysiological mechanisms
Vaněčková, I., Maletı́nská, L., Behuliak, M., Pražienková, V., Zicha, J., & Kuneš, J. (2014) · Journal of Endocrinology · doi:10.1530/joe-14-0368 · Cited by 168
A brain leptin-renin angiotensin system interaction in the regulation of sympathetic nerve activity
Hilzendeger, A. M., Morgan, D. A., Brooks, L. A., Dellsperger, D., Liu, X., Grobe, J. L., Rahmouni, K., Sigmund, C. D., & Mark, A. L. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00974.2011 · Cited by 118
Metadata
- Authors
- Prior, L. J., Eikelis, N., Armitage, J. A., Davern, P. J., Burke, S. L., Montani, J.-P., Barzel, B., & Head, G. A.
- Affiliations
- Baker Heart and Diabetes Institute (AU)
- Venue
- Hypertension
- Published
- 2010-04
- Volume
- 55
- Issue
- 4
- Pages
- 862-868
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2073599743
- Cited by
- 157
- References
- 42
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 4 · 2022: 5 · 2021: 9 · 2020: 10 · 2019: 9 · 2018: 6 · 2017: 11 · 2016: 12 · 2015: 16 · 2014: 14 · 2013: 21 · 2012: 16
- FWCI
- 8.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- reroDoc Digital Library (submittedVersion)
- Deakin Research Online (Deakin University) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- high-fat diet, leptin, leptin resistance, renal sympathetic nerve activity, visceral fat, obesity, sympathetic nervous system, c-fos, hypothalamus, norepinephrine, arterial pressure, rabbits
- MeSH terms
- Analysis of Variance, Animals, Blood Pressure, Body Weight, Catheters, Indwelling, Dietary Fats, Dose-Response Relationship, Drug, Heart Rate, Hypothalamus, Injections, Intraventricular, Kidney, Male, Neurons, Rabbits, Sympathetic Nervous System, Proto-Oncogene Proteins c-fos, Leptin, Intra-Abdominal Fat, Receptors, Leptin
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