Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits

Prior, Larissa J., Eikelis, Nina, Armitage, James A., Davern, Pamela J., Burke, Sandra L., Montani, Jean-Pierre, Barzel, Benjamin and Head, Geoffrey A. 2010, Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits, Hypertension, vol. 55, no. 4, pp. 862-868, doi: 10.1161/HYPERTENSIONAHA.109.141119.

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Title Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits
Author(s) Prior, Larissa J.
Eikelis, Nina
Armitage, James A.ORCID iD for Armitage, James A. orcid.org/0000-0002-3762-0911
Davern, Pamela J.
Burke, Sandra L.
Montani, Jean-Pierre
Barzel, Benjamin
Head, Geoffrey A.
Journal name Hypertension
Volume number 55
Issue number 4
Start page 862
End page 868
Total pages 7
Publisher Lippincott Williams & Wilkins
Place of publication Philadelphia, Pa.
Publication date 2010-04
ISSN 0194-911X
Keyword(s) obesity-related hypertension
sympathetic nervous system
leptin resistance
New Zealand white rabbit
Summary 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.
Language eng
DOI 10.1161/HYPERTENSIONAHA.109.141119
Field of Research 179999 Psychology and Cognitive Sciences not elsewhere classified
Socio Economic Objective 970117 Expanding Knowledge in Psychology and Cognitive Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2010, Lippincott Williams & Wilkins
Persistent URL http://hdl.handle.net/10536/DRO/DU:30064852

Document type: Journal Article
Collection: School of Medicine
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