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SHR Neuro Cancer Cardio Lipid Metab Microb
Tamilarasan, KP; Temmel, H; Das, SK; Al Zoughbi, W; Schauer, S; Vesely, PW; Hoefler, G.
Skeletal muscle damage and impaired regeneration due to LPL-mediated lipotoxicity.
Cell Death Dis. 2012; 3(11):e354-e354
Doi: 10.1038/cddis.2012.91
[OPEN ACCESS]
Web of Science
PubMed
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FullText_MUG
- Leading authors Med Uni Graz
- Höfler Gerald
- Kuppusamy Palaniappan Tamilarasan
- Vesely Paul
- Co-authors Med Uni Graz
- Al-Zoughbi Wael
- Das Suman Kumar
- Schauer Silvia
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- Dimensions Citations:
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- Abstract:
- According to the concept of lipotoxicity, ectopic accumulation of lipids in non-adipose tissue induces pathological changes. The most prominent effects are seen in fatty liver disease, lipid cardiomyopathy, non-insulin-dependent diabetes mellitus, insulin resistance and skeletal muscle myopathy. We used the MCK(m)-hLPL mouse distinguished by skeletal and cardiac muscle-specific human lipoprotein lipase (hLPL) overexpression to investigate effects of lipid overload in skeletal muscle. We were intrigued to find that ectopic lipid accumulation induced proteasomal activity, apoptosis and skeletal muscle damage. In line with these findings we observed reduced Musculus gastrocnemius and Musculus quadriceps mass in transgenic animals, accompanied by severely impaired physical endurance. We suggest that muscle loss was aggravated by impaired muscle regeneration as evidenced by reduced cross-sectional area of regenerating myofibers after cardiotoxin-induced injury in MCK(m)-hLPL mice. Similarly, an almost complete loss of myogenic potential was observed in C2C12 murine myoblasts upon overexpression of LPL. Our findings directly link lipid overload to muscle damage, impaired regeneration and loss of performance. These findings support the concept of lipotoxicity and are a further step to explain pathological effects seen in muscle of obese patients, patients with the metabolic syndrome and patients with cancer-associated cachexia.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis -
- Cell Line -
- Creatine Kinase - genetics Creatine Kinase - metabolism
- Fatty Acids - metabolism
- Humans -
- Lipoprotein Lipase - genetics Lipoprotein Lipase - metabolism
- Mice -
- Mice, Inbred C57BL -
- Mice, Transgenic -
- Muscle, Skeletal - metabolism
- Myoblasts - metabolism
- Regeneration -
- Triglycerides - metabolism
- Find related publications in this database (Keywords)
- lipotoxicity
- lipoprotein lipase
- muscle atrophy
- muscle regeneration