Diet-induced obesity in Sprague-Dawley rats causes microvascular and neural dysfunction

Eric P Davidson; Lawrence J Coppey; Nigel A Calcutt; Christine L Oltman; Mark A Yorek

doi:10.1002/dmrr.1088

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Diet-induced obesity in Sprague-Dawley rats causes microvascular and neural dysfunction

Journal article

Open access

Diet-induced obesity in Sprague-Dawley rats causes microvascular and neural dysfunction

Eric P Davidson, Lawrence J Coppey, Nigel A Calcutt, Christine L Oltman and Mark A Yorek

Diabetes/Metabolism Research and Reviews, Vol.26(4), pp.306-318

05/2010

DOI: 10.1002/dmrr.1088

PMCID: PMC2878284

PMID: 20503263

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Abstract

Background: The objective of this study was to determine the effect of diet-induced obesity (DIO) on microvascular and neural function. Methods: Rats were fed a standard or high fat diet for up to 32 weeks. The following measurements were carried out: vasodilation in epineurial arterioles using videomicroscopy, endoneurial blood flow using hydrogen clearance, nerve conduction velocity using electrical stimulation, size-frequency distribution of myelinated fibres of the sciatic nerve, intraepidermal nerve fibre density using confocal microscopy and thermal nociception using the Hargreaves method. Results: Rats fed a high fat diet for 32 weeks developed sensory neuropathy, as indicated by slowing of sensory nerve conduction velocity and thermal hypoalgesia. Motor nerve conduction velocity and endoneurial blood flow were not impaired. Mean axonal diameter of myelinated fibres of the sciatic nerve was unchanged in high fat-fed rats compared with that in control. Intraepidermal nerve fibre density was significantly reduced in high fat-fed rats. Vascular relaxation to acetylcholine and calcitonin gene-related peptide was decreased and expression of neutral endopeptidase (NEP) increased in epineurial arterioles of rats fed a high fat diet. In contrast, insulin-mediated vascular relaxation was increased in epineurial arterioles. NEP activity was significantly increased in the skin of the hindpaw. Markers of oxidative stress were increased in the aorta and serum of high fat-fed rats but not in epineurial arterioles. Conclusion: Chronic obesity causes microvascular and neural dysfunction. This is associated with increased expression of NEP but not oxidative stress in epineurial arterioles. NEP degrades vasoactive peptides, which may explain the decrease in microvascular function.

Obesity

vascular function

neuropathy

neutral endopeptidase

Details

Title: Subtitle: Diet-induced obesity in Sprague-Dawley rats causes microvascular and neural dysfunction
Creators: Eric P Davidson - Veteran Affairs Medical Center, University of Iowa, Iowa City, IA, USA
Lawrence J Coppey - Veteran Affairs Medical Center, University of Iowa, Iowa City, IA, USA
Nigel A Calcutt - Department of Pathology, University of California San Diego, CA, USA
Christine L Oltman - Veteran Affairs Medical Center, University of Iowa, Iowa City, IA, USA
Mark A Yorek - Veteran Affairs Medical Center, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Diabetes/Metabolism Research and Reviews, Vol.26(4), pp.306-318
DOI: 10.1002/dmrr.1088
PMID: 20503263
PMCID: PMC2878284
NLM abbreviation: Diabetes Metab Res Rev
ISSN: 1520-7552
eISSN: 1099-0895
Publisher: John Wiley & Sons, Ltd
Number of pages: 13
Language: English
Date published: 05/2010
Academic Unit: Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984094676602771

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