Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Levak-Frank, S; Radner, H; Walsh, A; Stollberger, R; Knipping, G; Hoefler, G; Sattler, W; Weinstock, PH; Breslow, JL; Zechner, R.
Muscle-specific overexpression of lipoprotein lipase causes a severe myopathy characterized by proliferation of mitochondria and peroxisomes in transgenic mice.
J Clin Invest. 1995; 96(2):976-986
Doi: 10.1172/JCI118145
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- Führende Autor*innen der Med Uni Graz
- Levak Sanja
- Co-Autor*innen der Med Uni Graz
- Höfler Gerald
- Sattler Wolfgang
- Stollberger Rudolf
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- Abstract:
- In extrahepatic tissues lipoprotein lipase (LPL) hydrolyzes triglycerides thereby generating FFA for tissue uptake and metabolism. To study the effects of increased FFA uptake in muscle tissue, transgenic mouse lines were generated with a human LPL minigene driven by the promoter of the muscle creatine kinase gene. In these mice human LPL was expressed in skeletal muscle and cardiac muscle, but not in other tissues. In proportion to the level of LPL overexpression, decreased plasma triglyceride levels, elevated FFA uptake by muscle tissue, weight loss, and premature death were observed in three independent transgenic mouse lines. The animals developed a severe myopathy characterized by muscle fiber degeneration, fiber atrophy, glycogen storage, and extensive proliferation of mitochondria and peroxisomes. This degree of proliferation suggests that FFA play an important role in the biogenesis of these organelles. Our experiments indicate that LPL is rate limiting for the supply of muscle tissue with triglyceride-derived FFA. Improper regulation of muscle LPL can lead to major pathological changes and may be important in the pathogenesis of some human myopathies. Muscle-specific LPL transgenic mouse lines will serve as a useful animal model for the investigation of myopathies and the biogenesis of mitochondria and peroxisomes.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Creatine Kinase - genetics
- Enzyme Induction - genetics
- Fatty Acids, Nonesterified - metabolism
- Genes, Synthetic - metabolism
- Glucose - metabolism
- Humans - metabolism
- Lipolysis - metabolism
- Lipoprotein Lipase - biosynthesis
- Longevity - biosynthesis
- Magnetic Resonance Imaging - biosynthesis
- Mice - biosynthesis
- Mice, Inbred C57BL - biosynthesis
- Mice, Inbred CBA - biosynthesis
- Mice, Transgenic - biosynthesis
- Microbodies - pathology
- Mitochondria, Muscle - pathology
- Mitochondrial Myopathies - enzymology
- Muscle Proteins - biosynthesis
- Muscles - metabolism
- Organ Specificity - metabolism
- Promoter Regions (Genetics) - metabolism
- Recombinant Fusion Proteins - biosynthesis
- Triglycerides - blood
- Weight Loss - blood
- Find related publications in this database (Keywords)
- Lipoprotein Lipase
- Free Fatty Acids
- Myopathy
- Mitochondria
- Peroxisomes