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 overexpression 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.