Document Detail

Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet.
MedLine Citation:
PMID:  20702796     Owner:  NLM     Status:  MEDLINE    
Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.
Jill K Morris; Gregory L Bomhoff; John A Stanford; Paige C Geiger
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-08-11
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  299     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-01     Completed Date:  2010-10-19     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1082-90     Citation Subset:  IM    
Department of Molecular and Integrative Physiology, Univ. of Kansas Medical Center, Kansas City, 66160, USA.
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MeSH Terms
Blood Glucose / metabolism
Body Weight / physiology
Cholesterol / blood
Chromatography, High Pressure Liquid
Dietary Fats / toxicity*
Dopamine / physiology
Eating / physiology
Epididymis / metabolism
Glucose Tolerance Test
Hydrogen Peroxide
Insulin / blood
Insulin Resistance / physiology
Iron / metabolism
Muscle, Skeletal / metabolism
Neostriatum / physiology
Nerve Degeneration / pathology*
Neurons / physiology
Parkinson Disease, Secondary / chemically induced,  pathology*
Rats, Inbred F344
Substantia Nigra / physiology
Grant Support
Reg. No./Substance:
0/Blood Glucose; 0/Dietary Fats; 0/Fenton's reagent; 0/Insulin; 0/Sympatholytics; 1199-18-4/Oxidopamine; 57-88-5/Cholesterol; 7439-89-6/Iron; 7722-84-1/Hydrogen Peroxide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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