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Selected Publication:
Strauss, JG; Frank, S; Kratky, D; Hämmerle, G; Hrzenjak, A; Knipping, G; von Eckardstein, A; Kostner, GM; Zechner, R.
Adenovirus-mediated rescue of lipoprotein lipase-deficient mice. Lipolysis of triglyceride-rich lipoproteins is essential for high density lipoprotein maturation in mice.
J Biol Chem. 2001; 276(39):36083-36090
Doi: 10.1074/jbc.M104430200
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- Co-authors Med Uni Graz
- Frank Sasa
- Hrzenjak Andelko
- Kostner Gerhard
- Kratky Dagmar
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- Abstract:
- Lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of triglycerides and the subsequent uptake of free fatty acids in extrahepatic tissues. Deficiency of LPL in humans (Type I hyperlipoproteinemia) is associated with massive chylomicronemia, low high density lipoprotein (HDL) cholesterol levels, and recurrent attacks of pancreatitis when not controlled by a strict diet. In contrast to humans, homozygous LPL knock-out mice (L0) do not survive suckling and die between 18 and 24 h after birth. In this study, an adenovirus-based protocol was utilized for the transient expression of LPL during the suckling period in an effort to rescue L0 mice. After a single intraperitoneal injection of 5x10(9) plaque-forming units of LPL-expressing virus immediately after birth, more than 90% of L0 mice survived the first days of life. 3% of L0 mice survived the entire suckling period and lived for up to 20 months, although LPL activity in mouse tissues and postheparin plasma was undetectable in all animals after 6 weeks of age. Adult LPL-deficient mice were smaller than their littermates until 2-3 months of age and exhibited very high triglyceride levels in the fed (4997 +/- 1102 versus 113.4 +/- 18.7 mg/dl) and fasted state (2007 +/- 375 versus 65.5 +/- 7.4 mg/dl). Plasma total cholesterol levels, free fatty acids, and ketone bodies were elevated in L0 mice, whereas plasma glucose was normal. Most strikingly, L0 mice lacked apoA-I-containing prebeta-HDL particles as well as mature HDL resulting in undetectable HDL cholesterol and HDL-apoA-I levels. HDL deficiency in plasma was evident despite normal apoA-I mRNA levels in the liver and normal apoA-I protein levels in plasma, which were predominantly found in the chylomicron fraction. The absence of prebeta-HDL and mature HDL particles supports the concept that the lipolysis of triglyceride-rich lipoproteins is an essential step for HDL maturation.
- Find related publications in this database (using NLM MeSH Indexing)
- Adenoviridae - genetics
- Animals - genetics
- Blood Glucose - metabolism
- Blotting, Western - metabolism
- Body Weight - metabolism
- Cholesterol - blood
- DNA, Complementary - metabolism
- Fatty Acids, Nonesterified - blood
- Hydrolysis - blood
- Ketones - blood
- Lipoprotein Lipase - genetics
- Lipoproteins, HDL - metabolism
- Liver - metabolism
- Mice - metabolism
- Mice, Knockout - metabolism
- RNA - metabolism
- RNA, Messenger - metabolism
- Time Factors - metabolism
- Triglycerides - blood