The role of the kidney in lipid metabolism.
OBJECTIVE
Cellular uptake of plasma lipids is to a large extent mediated by specific membrane-associated proteins that recognize lipid-protein complexes. In the kidney, the apical surface of proximal tubules has a high capacity for receptor-mediated uptake of filtered lipid-binding plasma proteins. We describe the renal receptor system and its role in lipid metabolism in health and disease, and discuss the general effect of the diseased kidney on lipid metabolism.


RESULTS
Megalin and cubilin are receptors in the proximal tubules. An accumulating number of lipid-binding and regulating proteins (e.g. albumin, apolipoprotein A-I and leptin) have been identified as ligands, suggesting that their receptors may directly take up lipids in the proximal tubules and indirectly affect plasma and tissue lipid metabolism. Recently, the amnionless protein was shown to be essential for the membrane association and trafficking of cubilin.


CONCLUSIONS
The kidney has a high capacity for uptake of lipid-binding proteins and lipid-regulating hormones via the megalin and cubilin/amnionless protein receptors. Although the glomerular filtration barrier prevents access of the large lipoprotein particles to the proximal tubules, the receptors may be exposed to lipids bound to filtered lipid-binding proteins not associated to lipoprotein particles. Renal filtration and receptor-mediated uptake of lipid-binding and lipid-regulating proteins may therefore influence overall lipid metabolism. The pathological mechanisms causing the pronounced atherosclerosis-promoting effect of uremia may involve impairment of this clearance pathway.
Moestrup
Søren K
SK
Department of Medical Biochemistry, University of Aarhus, Denmark. skm@biokemi.au.dk
Nielsen
Lars Bo
LB
D005919:Glomerular Filtration Rate; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000502:physiology*; D008024:Ligands; D050356:Lipid Metabolism; D026561:Low Density Lipoprotein Receptor-Related Protein-2 / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*
D008024:Ligands; D026561:Low Density Lipoprotein Receptor-Related Protein-2; D011956:Receptors, Cell Surface; C029486:intrinsic factor-cobalamin receptor