Document Detail


Diet-induced obesity in Sprague-Dawley rats causes microvascular and neural dysfunction.
MedLine Citation:
PMID:  20503263     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Eric P Davidson; Lawrence J Coppey; Nigel A Calcutt; Christine L Oltman; Mark A Yorek
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Diabetes/metabolism research and reviews     Volume:  26     ISSN:  1520-7560     ISO Abbreviation:  Diabetes Metab. Res. Rev.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-26     Completed Date:  2011-02-08     Revised Date:  2011-07-28    
Medline Journal Info:
Nlm Unique ID:  100883450     Medline TA:  Diabetes Metab Res Rev     Country:  England    
Other Details:
Languages:  eng     Pagination:  306-18     Citation Subset:  IM    
Affiliation:
Veteran Affairs Medical Center, University of Iowa, Iowa City, IA 52246, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Arterioles / physiopathology*
Blood Glucose / metabolism
Blotting, Western
Immunohistochemistry
Nervous System Diseases / etiology*,  physiopathology
Obesity / complications*,  etiology,  physiopathology
Rats
Rats, Sprague-Dawley
Grant Support
ID/Acronym/Agency:
DK057629/DK/NIDDK NIH HHS; DK073990/DK/NIDDK NIH HHS; R01 DK073990-02/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose
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