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Liver-specific loss of lipolysis-stimulated lipoprotein receptor triggers systemic hyperlipidemia in mice

Title:
Liver-specific loss of lipolysis-stimulated lipoprotein receptor triggers systemic hyperlipidemia in mice
Abstract:
In mammals, proper storage and distribution of lipids in and between tissues is essential for the maintenance of energy homeostasis. In contrast, aberrantly high levels of triglycerides in the blood ("hypertriglyceridemia") represent a hallmark of the metabolic syndrome and type 2 diabetes. As hypertriglyceridemia has been identified as an important risk factor for cardiovascular complications, in this study we aimed to identify molecular mechanisms in aberrant triglyceride elevation under these conditions. To determine the importance of hepatic lipid handling for systemic dyslipidemia, we profiled the expression patterns of various hepatic lipid transporters and receptors under healthy and type 2 diabetic conditions. A differentially expressed lipoprotein receptor was functionally characterized by generating acute, liver-specific loss- and gain-of-function animal models. We show that the hepatic expression of lipid transporter lipolysis-stimulated lipoprotein receptor (LSR) is specifically impaired in mouse models of obesity and type 2 diabetes and can be restored by leptin replacement. Experimental imitation of this pathophysiological situation by liver-specific knockdown of LSR promotes hypertriglyceridemia and elevated apolipoprotein (Apo)B and E serum levels in lean wild-type and ApoE knockout mice. In contrast, genetic restoration of LSR expression in obese animals to wild-type levels improves serum triglyceride levels and serum profiles in these mice. The dysregulation of hepatic LSR under obese and diabetic conditions may provide a molecular rationale for systemic dyslipidemia in type 2 diabetes and the metabolic syndrome and represent a novel target for alternative treatment strategies in these patients.
Year:
2009
Publication type:
Journal article
Journal:
Diabetes
ISSN:
1939-327X
Number:
5
Volume:
58
Pages:
1040-1049
Language:
English
Document status:
Published
PubListerURL:
https://publister.bib.th-wildau.de/publister/public/publication/461
Narvekar, P., Berriel Diaz, M., Krones-Herzig, A., Hardeland, U., Strzoda, D., Stöhr, S., et al. (2009). Liver-specific loss of lipolysis-stimulated lipoprotein receptor triggers systemic hyperlipidemia in mice Diabetes. 58 (5), 1040-1049.
@article{461,
    author           = {Narvekar, Prachiti and Berriel Diaz, Mauricio and Krones-Herzig, Anja and Hardeland, Ulrike and Strzoda, Daniela and Stöhr, Sigrid and Frohme, Marcus and Herzig, Stephan},
    title            = {Liver-specific loss of lipolysis-stimulated lipoprotein receptor triggers systemic hyperlipidemia in mice},
    journal          = {Diabetes},
    year             = {2009},
    volume           = {58},
    number           = {5},
    pages            = {1040-1049},
    doi              = {10.2337/db08-1184},
}


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