Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Levak-Frank, S; Hofmann, W; Weinstock, PH; Radner, H; Sattler, W; Breslow, JL; Zechner, R.
Induced mutant mouse lines that express lipoprotein lipase in cardiac muscle, but not in skeletal muscle and adipose tissue, have normal plasma triglyceride and high-density lipoprotein-cholesterol levels.
Proc Natl Acad Sci U S A. 1999; 96(6):3165-3170
Doi: 10.1073%2Fpnas.96.6.3165
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- Führende Autor*innen der Med Uni Graz
- Levak Sanja
- Co-Autor*innen der Med Uni Graz
- Sattler Wolfgang
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- Abstract:
- The tissue-specific expression of lipoprotein lipase (LPL) in adipose tissue (AT), skeletal muscle (SM), and cardiac muscle (CM) is rate-limiting for the uptake of triglyceride (TG)-derived free fatty acids and decisive in the regulation of energy balance and lipoprotein metabolism. To investigate the tissue-specific metabolic effects of LPL, three independent transgenic mouse lines were established that expressed a human LPL (hLPL) minigene predominantly in CM. Through cross-breeding with heterozygous LPL knockout mice, animals were generated that produced hLPL mRNA and enzyme activity in CM but lacked the enzyme in SM and AT because of the absence of the endogenous mouse LPL gene (L0-hLPL). LPL activity in CM and postheparin plasma of L0-hLPL mice was reduced by 34% and 60%, respectively, compared with control mice. This reduced LPL expression was sufficient to rescue LPL knockout mice from neonatal death. L0-hLPL animals developed normally with regard to body weight and body-mass composition. Plasma TG levels in L0-hLPL animals were increased up to 10-fold during the suckling period but normalized after weaning and decreased in adult animals. L0-hLPL mice had normal plasma high-density lipoprotein (HDL)-cholesterol levels, indicating that LPL expression in CM alone was sufficient to allow for normal HDL production. The absence of LPL in SM and AT did not cause detectable morphological or histopathological changes in these tissues. However, the lipid composition in AT and SM exhibited a marked decrease in polyunsaturated fatty acids. From this genetic model of LPL deficiency in SM and AT, it can be concluded that CM-specific LPL expression is a major determinant in the regulation of plasma TG and HDL-cholesterol levels.
- Find related publications in this database (using NLM MeSH Indexing)
- Adipose Tissue - metabolism
- Animals - metabolism
- Body Weight - metabolism
- Cholesterol, HDL - blood
- Disease Models, Animal - blood
- Gene Expression Regulation - blood
- Humans - blood
- Lipoprotein Lipase - biosynthesis
- Mice - biosynthesis
- Mice, Mutant Strains - biosynthesis
- Mice, Transgenic - biosynthesis
- Muscle, Skeletal - metabolism
- Myocardium - metabolism
- Organ Specificity - metabolism
- Transfection - metabolism
- Triglycerides - blood