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

  • Prior, Larissa J. Baker IDI Heart and Diabetes Institute, Melbourne, Australia - Melbourne, Australia
  • Eikelis, Nina Baker IDI Heart and Diabetes Institute, Melbourne, Australia
  • Armitage, James A. Baker IDI Heart and Diabetes Institute, Melbourne, Australia - Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
  • Davern, Pamela J. Baker IDI Heart and Diabetes Institute, Melbourne, Australia
  • Burke, Sandra L. Baker IDI Heart and Diabetes Institute, Melbourne, Australia
  • Montani, Jean-Pierre Department of Medicine/Physiology, University of Fribourg, Fribourg, Switzerland
  • Barzel, Benjamin Baker IDI Heart and Diabetes Institute, Melbourne, Australia - Department of Anatomy and Developmental Biology, Monash University, Clayton, Victoria, Australia
  • Head, Geoffrey A. Baker IDI Heart and Diabetes Institute, Melbourne, Australia
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    01.03.2010
Published in:
  • Hypertension. - 2010, vol. 55, no. 4, p. 862-868
obesity-related hypertension
sympathetic nervous system
hypothalamus
leptin
leptin resistance
New Zealand white rabbit
English 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.
Faculty
Faculté des sciences et de médecine
Department
Département de Médecine
Language
  • English
Classification
Biological sciences
License
License undefined
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Persistent URL
https://folia.unifr.ch/unifr/documents/301568
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