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Published on: November 16, 2011
Insulin deficiency and reduced expression of lipogenic enzymes in cardiomyopathic hamster
A Vecchini1, L Binaglia, M Bibeau
1Institute of Biochemistry, Faculty of Medicine, University of Perugia, 06126 Perugia, Italy.
Insights
Cardiomyopathic hamsters exhibit widespread lipid metabolism disturbances, including reduced lipogenic enzyme activity and impaired gene expression. This metabolic defect is linked to low insulin levels in affected animals.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Metabolic Research
Background:
- The cardiomyopathic UM-X7.1 hamster model displays distinct lipid profiles in cardiac and non-cardiac tissues compared to healthy controls.
- Preliminary observations suggest a generalized disturbance in lipid metabolism in cardiomyopathic hamsters.
Purpose of the Study:
- To investigate hepatic lipid biosynthesis in cardiomyopathic versus healthy Syrian hamsters.
- To identify the molecular mechanisms underlying lipid metabolism alterations in cardiomyopathy.
Main Methods:
- Comparative analysis of hepatic lipid composition and enzyme activities (fatty acid synthase, stearoyl-CoA desaturase).
- Northern blot analysis to assess mRNA levels of lipogenic enzymes and S14 nuclear protein.
- Evaluation of dietary influences on gene expression in both hamster groups.
Main Results:
- Cardiomyopathic hamsters showed significantly lower fatty acid synthase and stearoyl-CoA desaturase activities in the liver.
- Impaired gene transcription for key lipogenic enzymes was observed in UM-X7.1 hamsters.
- Dietary carbohydrates were less effective in inducing lipogenic enzyme expression in cardiomyopathic livers.
Conclusions:
- The cardiomyopathic hamster model is characterized by a generalized disruption of lipid metabolism.
- Reduced expression of lipogenic enzymes and impaired gene transcription are key features.
- Low plasma insulin levels appear to be the primary determinant of the observed metabolic defect.
Abstract:
Evidence is given that the heart of the cardiomyopathic UM-X7.1 hamster has a lipid composition different from that of the same tissue isolated from animals of the Syrian hamster parent strain. Also, noncardiac tissues from cardiomyopathic and healthy hamsters exhibit significant compositional differences. On the basis of these preliminary observations, a comparative study of the hepatic biosynthesis of lipids in cardiomyopathic and healthy Syrian hamsters was undertaken. The results obtained indicate that the cardiomyopathic hamster is characterized by a generalized disturbance of lipid metabolism. In particular, the fatty acid synthase and stearoyl-CoA desaturase activities were significantly lower in the liver of UM-X7.1 hamsters than in age-matched healthy controls fed the same diet. Northern blot analysis of the mRNAs encoding the two enzymatic proteins and the "lipogenic" S14 nuclear protein indicated that the transcription of the respective genes was impaired in UM-X7.1.Short-term dietary manipulations modulated the expression of the above-mentioned genes both in cardiomyopathic and healthy animals. However, dietary carbohydrates were less effective in inducing the expression of lipogenic enzymes in UM-X7.1 liver than healthy controls. The main determinant of the metabolic defect pointed out in the present work appears to be represented by the low insulin level detectable in the plasma of the cardiomyopathic hamster.-Vecchini, A., L. Binaglia, M. Bibeau, M. Minieri, F. Carotenuto, and P. Di Nardo. Insulin deficiency and reduced expression of lipogenic enzymes in cardiomyopathic hamster. J. Lipid Res. 2001. 42: 96;-105.
