Medizinische Universität Graz - Research portal

Go directly to the nagivation.
Go directly to the content.

Navigation/Search

Selected Publication:

Hoefler, G; Noehammer, C; Levak-Frank, S; el-Shabrawi, Y; Schauer, S; Zechner, R; Radner, H.
Muscle-specific overexpression of human lipoprotein lipase in mice causes increased intracellular free fatty acids and induction of peroxisomal enzymes.
Biochimie. 1997; 79(2-3):163-168 Doi: 10.1016%2FS0300-9084%2897%2981509-X
Web of Science PubMed FullText FullText_MUG Google Scholar

Leading authors Med Uni Graz: Höfler Gerald
Co-authors Med Uni Graz: El-Shabrawi Yosuf; Levak Sanja
Altmetrics:
Dimensions Citations:
Plum Analytics:
Scite (citation analytics):
Abstract:: A transgenic mouse model for peroxisomal and mitochondrial induction caused by increased uptake of fatty acids in muscle was established. Transgenic mouse lines were generated using a human lipoprotein lipase (LPL) mini gene (3-20 copies) driven by the promoter of the muscle creatine kinase gene. Expression of human LPL was only observed in skeletal and cardiac muscle. In proportion to the level of LPL overexpression increased LPL activity in skeletal (up to 24-fold) and cardiac (up to three-fold) muscle, decreased plasma triglyceride levels, elevated free fatty acid (FFA) uptake by muscle tissue, weight loss (due to a reduction in muscle mass as well as adipose tissue mass) and premature death were observed. A remarkable increase in the number of mitochondria and peroxisomes was detected using oxide-electron microscopy. Proliferation of mitochondria and peroxisomes was confirmed by a dose-dependent increase of marker enzyme activity (succinate-dehydrogenase and catalase). In addition, peroxisomal acyl-CoAse enzyme protein was markedly elevated whereas mRNA was increased only up to two-fold. No changes in peroxisomal proliferator activated receptor alpha mRNA was found. This degree of proliferation and enzyme activity of mitochondria and peroxisomes suggests that FFA play an important role in the induction of these organelles. In addition, myopathy characterized by excessive glycogen storage, muscle fiber degeneration, and fiber atrophy with centralization of nuclei, mimicking several forms of human myopathies was noted. Our results imply that improper regulation of muscle LPL leading to increased fatty acid levels in muscle can cause severe pathological changes. This effect may be important in the pathogenesis of human myopathies. We conclude that these transgenic mouse lines could serve as a useful animal model for the investigation of myopathies and the effects of fatty acids on the induction of mitochondria and peroxisomes.
Find related publications in this database (using NLM MeSH Indexing): Animals -; Body Composition -; Body Weight -; Cytoplasm - metabolism; Enzyme Induction - metabolism; Fatty Acids, Nonesterified - metabolism; Humans - metabolism; Lipid Metabolism - metabolism; Lipoprotein Lipase - metabolism; Mice - metabolism; Mice, Transgenic - metabolism; Microbodies - enzymology; Microscopy, Electron - enzymology; Mitochondria, Muscle - metabolism; Muscle Proteins - metabolism; Muscles - anatomy and histology
Find related publications in this database (Keywords): Peroxisomes; Lipoprotein Lipase; Free Fatty Acids; Beta-Oxidation; Myopathy; Transgenic Mouse Model