Hepatic lipase: structure/function relationship, synthesis, and regulation.
Hepatic lipase (HL) is a lipolytic enzyme, synthesized by hepatocytes and found localized at the surface of liver sinusoid capillaries. In humans, the enzyme is mostly bound onto heparan-sulfate proteoglycans at the surface of hepatocytes and also of sinusoid endothelial cells. HL shares a number of functional domains with lipoprotein lipase and with other members of the lipase gene family. It is a secreted glycoprotein, and remodelling of the N-linked oligosaccharides appears to be crucial for the secretion process, rather than for the acquisition of the catalytic activity. HL is also present in adrenals and ovaries, where it might promote delivery of lipoprotein cholesterol for steroidogenesis. However, evidence of a local synthesis is still controversial. HL activity is fairly regulated according to the cell cholesterol content and to the hormonal status. Coordinate regulations have been reported for both HL and the scavenger-receptor B-I, suggesting complementary roles in cholesterol metabolism. However, genetic variants largely contribute to HL variability and their possible impact in the development of a dyslipidemic phenotype, or in a context of insulin-resistance, is discussed.
Perret
Bertrand
B
Institut National de la Santé et de la Recherche Médicale, Unité 563, Department of Lipoproteins and Lipid Mediators, Institut Fédératif IFR 30, Hôpital Purpan, 31059 Toulouse Cedex, France. perret@toulouse.inserm.fr
Mabile
Laurence
L
Martinez
Laurent
L
Tercé
François
F
Barbaras
Ronald
R
Collet
Xavier
X
D000595:Amino Acid Sequence; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008049:Lipase / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
D008049:Lipase