Linked Life Data

11432868

Source:http://linkedlifedata.com/resource/pubmed/id/11432868

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
39
pubmed:dateCreated
2001-9-24
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
276
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36083-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11432868-Adenoviridae, pubmed-meshheading:11432868-Animals, pubmed-meshheading:11432868-Blood Glucose, pubmed-meshheading:11432868-Blotting, Western, pubmed-meshheading:11432868-Body Weight, pubmed-meshheading:11432868-Cholesterol, pubmed-meshheading:11432868-DNA, Complementary, pubmed-meshheading:11432868-Fatty Acids, Nonesterified, pubmed-meshheading:11432868-Hydrolysis, pubmed-meshheading:11432868-Ketones, pubmed-meshheading:11432868-Lipoprotein Lipase, pubmed-meshheading:11432868-Lipoproteins, HDL, pubmed-meshheading:11432868-Liver, pubmed-meshheading:11432868-Mice, pubmed-meshheading:11432868-Mice, Knockout, pubmed-meshheading:11432868-RNA, pubmed-meshheading:11432868-RNA, Messenger, pubmed-meshheading:11432868-Time Factors, pubmed-meshheading:11432868-Triglycerides
pubmed:year
2001
pubmed:articleTitle
Adenovirus-mediated rescue of lipoprotein lipase-deficient mice. Lipolysis of triglyceride-rich lipoproteins is essential for high density lipoprotein maturation in mice.
pubmed:affiliation
Institute of Molecular Biology, Biochemistry, and Microbiology, University of Graz, Graz A-8010, Austria.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't