Muscle-specific overexpression of lipoprotein lipase in transgenic mice results in increased alpha-tocopherol levels in skeletal muscle

Biochem J. 1996 Aug 15;318 ( Pt 1)(Pt 1):15-9. doi: 10.1042/bj3180015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Brain / metabolism
  • Centrifugation, Density Gradient
  • Fatty Acids, Nonesterified / metabolism
  • Gene Dosage
  • Gene Expression*
  • Heparin / pharmacology
  • Lipoprotein Lipase / biosynthesis
  • Lipoprotein Lipase / genetics*
  • Lipoproteins / blood
  • Mice
  • Mice, Transgenic
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / metabolism*
  • Myocardium / metabolism
  • Vitamin E / blood
  • Vitamin E / metabolism*


  • Fatty Acids, Nonesterified
  • Lipoproteins
  • Vitamin E
  • Heparin
  • Lipoprotein Lipase