Document Detail


Cardiac and metabolic changes in long-term high fructose-fat fed rats with severe obesity and extensive intramyocardial lipid accumulation.
MedLine Citation:
PMID:  20357025     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Metabolic syndrome and obesity-related diseases are affecting more and more people in the Western world. The basis for an effective treatment of these patients is a better understanding of the underlying pathophysiology. Here, we characterize fructose- and fat-fed rats (FFFRs) as a new animal model of metabolic syndrome. Sprague-Dawley rats were fed a 60 kcal/100 kcal fat diet with 10% fructose in the drinking water. After 6, 12, 18, 24, 36, and 48 wk of feeding, blood pressure, glucose tolerance, plasma insulin, glucose, and lipid levels were measured. Cardiac function was examined by in vivo pressure volume measurements, and intramyocardial lipid accumulation was analyzed by confocal microscopy. Cardiac AMP-activated kinase (AMPK) and hepatic phosphoenolpyruvate carboxykinase (PEPCK) levels were measured by Western blotting. Finally, an ischemia-reperfusion study was performed after 56 wk of feeding. FFFRs developed severe obesity, decreased glucose tolerance, increased serum insulin and triglyceride levels, and an initial increased fasting glucose, which returned to control levels after 24 wk of feeding. The diet had no effect on blood pressure but decreased hepatic PEPCK levels. FFFRs showed significant intramyocardial lipid accumulation, and cardiac hypertrophy became pronounced between 24 and 36 wk of feeding. FFFRs showed no signs of cardiac dysfunction during unstressed conditions, but their hearts were much more vulnerable to ischemia-reperfusion and had a decreased level of phosphorylated AMPK at 6 wk of feeding. This study characterizes a new animal model of the metabolic syndrome that could be beneficial in future studies of metabolic syndrome and cardiac complications.
Authors:
Lene N Axelsen; Jacob B Lademann; J?rgen S Petersen; Niels-Henrik Holstein-Rathlou; Thorkil Ploug; Clara Prats; Henrik D Pedersen; Anne Louise Kj?lbye
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Publication Detail:
Type:  Journal Article     Date:  2010-03-31
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  298     ISSN:  1522-1490     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-25     Completed Date:  2010-06-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R1560-70     Citation Subset:  IM    
Affiliation:
Zealand Pharma A/S, Glostrup, Denmark. lax@mfi.ku.dk
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MeSH Terms
Descriptor/Qualifier:
AMP-Activated Protein Kinases / metabolism
Animals
Blood Pressure / drug effects
Fats / pharmacology*
Fructose / pharmacology*
Glucose / metabolism
Heart / drug effects
Insulin / blood
Lipids / blood
Liver / metabolism
Male
Metabolic Syndrome X / metabolism
Myocardium / metabolism
Obesity / metabolism*
Rats
Rats, Sprague-Dawley
Chemical
Reg. No./Substance:
0/Fats; 0/Lipids; 11061-68-0/Insulin; 30237-26-4/Fructose; 50-99-7/Glucose; EC 2.7.11.1/AMP-Activated Protein Kinases

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