Cited by 158Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesBlood Pressure and Hypertension Studies

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Exposure to a High-Fat Diet Alters Leptin Sensitivity and Elevates Renal Sympathetic Nerve Activity and Arterial Pressure in Rabbits

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Prior, Larissa J., Eikelis, Nina, Armitage, James A., Davern, Pamela J., Burke, Sandra L., Montani, Jean-Pierre, Barzel, Benjamin, Head, Geoffrey A.·2010·Hypertension

DOI 10.1161/hypertensionaha.109.141119

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Abstract

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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10.1161/hyp.25.4.560 · DOI
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10.1161/hyp.37.3.936 · DOI
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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)
ORCID: Eikelis, Nina
Armitage, James A.
Head, Geoffrey A.
Venue: Hypertension
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2010-04
Volume: 55
Issue: 4
Pages: 862-868
ISSN: 0194-911X (ISSN-L)
1524-4563
DOI: 10.1161/hypertensionaha.109.141119
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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Exposure to a High-Fat Diet Alters Leptin Sensitivity and Elevates Renal Sympathetic Nerve Activity and Arterial Pressure in Rabbits

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