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 chylom icron-located alpha-tocopherol (alpha-TocH) to peripheral tissues, To investigate the role of LPL in the cellular uptake of alpha-TocH in pe ripheral tissue in vivo, three lines of transgenic mice [mouse creatin e kinase- (MCK) L, MCK-M and MCK-H] expressing various amounts of huma n LPL were compared with regard to alpha-TocH levels in plasma, skelet al 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 intrac ellular levels of alpha-TocH in skeletal muscle were significantly inc reased in MCK-M and MCK-H animals and correlated highly with the tissu e-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). Excellen t correlation was also observed between intracellular alpha-TocH and n on-esterified fatty acid (NEFA) levels (r = 0.998), Although LPL activ ities in cardiac muscle were also increased in the transgenic mouse li nes, alpha-TocH concentrations in the heart remained unchanged. Simila rly, alpha-TocH levels in plasma, adipose tissue and brain were unaffe cted by the tissue specific overexpression of LPL in muscle. The trans genic model presented in this report provides evidence that the uptake of alpha-TocH in muscle is directly dependent on the level of LPL exp ression in vivo. Increased intracellular alpha-TocH concentrations wit h increased triglyceride lipolysis and NEFA uptake might protect the m yocyte from oxidative damage during increased beta-oxidation.