Muscle-specific overexpression of lipoprotein lipase in transgenic mice results in increased alpha-tocopherol levels in skeletal muscle.
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.
Sattler
W
W
Department of Medical Biochemistry, University of Graz, Austria.
Levak-Frank
S
S
Radner
H
H
Kostner
G M
GM
Zechner
R
R
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism; D002499:Centrifugation, Density Gradient; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D018628:Gene Dosage; D015870:Gene Expression; D006493:Heparin / Q000494:pharmacology; D008071:Lipoprotein Lipase / Q000096:biosynthesis / Q000235:genetics*; D008074:Lipoproteins / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D014810:Vitamin E / Q000097:blood / Q000378:metabolism*
D005230:Fatty Acids, Nonesterified; D008074:Lipoproteins; D014810:Vitamin E; D006493:Heparin; D008071:Lipoprotein Lipase