Gewählte Publikation:
Sattler, W; Levak-Frank, S; Radner, H; Kostner, GM; Zechner, R.
Muscle-specific overexpression of lipoprotein lipase in transgenic mice results in increased alpha-tocopherol levels in skeletal muscle.
Biochem J. 1996; 318 ( Pt 1)(6):15-19
Doi: 10.1042/bj3180015
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- Führende Autor*innen der Med Uni Graz
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Sattler Wolfgang
- Co-Autor*innen der Med Uni Graz
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Kostner Gerhard
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Levak Sanja
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- Abstract:
- Lipoprotein lipase (LPL) has been implicated in the delivery of chylomicron-located alpha-tocopherol (alpha-TocH) to peripheral tissues. To investigate the role of LPL in the cellular uptake of alpha-TocH in peripheral tissue in vivo, three lines of transgenic mice [mouse creatine kinase- (MCK) L, MCK-M and MCK-H] expressing various amounts of human LPL were compared with regard to alpha-TocH levels in plasma, skeletal muscle, cardiac muscle, adipose tissue and brain. Depending on the copy number of the transgene, LPL activity was increased 3- to 27-fold in skeletal muscle and 1.3- to 3.7-fold in cardiac muscle. The intracellular levels of alpha-TocH in skeletal muscle were significantly increased in MCK-M and MCK-H animals and correlated highly with the tissue-specific LPL activity (r = 0.998). The highest levels were observed in MCK-H (21.4 nmol/g) followed by MCK-M (13.3 nmol/g) and MCK-L (8.2 nmol/g) animals when compared with control mice (7.3 nmol/g). Excellent correlation was also observed between intracellular alpha-TocH and non-esterified fatty acid (NEFA) levels (r = 0.998). Although LPL activities in cardiac muscle were also increased in the transgenic mouse lines, alpha-TocH concentrations in the heart remained unchanged. Similarly, alpha-TocH levels in plasma, adipose tissue and brain were unaffected by the tissue specific over-expression of LPL in muscle. The transgenic model presented in this report provides evidence that the uptake of alpha-TocH in muscle is directly dependent on the level of LPL expression in vivo. Increased intracellular alpha-TocH concentrations with increased triglyceride lipolysis and NEFA uptake might protect the myocyte from oxidative damage during increased beta-oxidation.
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Adipose Tissue - metabolism
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Animals - metabolism
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Brain - metabolism
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Centrifugation, Density Gradient - metabolism
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Fatty Acids, Nonesterified - metabolism
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Gene Dosage - metabolism
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Gene Expression - metabolism
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Heparin - pharmacology
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Lipoprotein Lipase - biosynthesis
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Lipoproteins - blood
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Mice - blood
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Mice, Transgenic - blood
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Muscle, Skeletal - enzymology
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Myocardium - metabolism
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Vitamin E - blood