Recent insights into factors affecting remnant lipoprotein uptake.
OBJECTIVE
Remnant lipoproteins that persist in the bloodstream after each meal have become increasingly important contributors to atherosclerotic vascular disease, owing to the spread of overnutrition, underexertion, obesity, insulin resistance, and type 2 diabetes. Here, we review recent work that clarified long-standing controversies over the molecular mediators of remnant clearance by the liver, as well as their dysregulation - but possible correction - during alterations in caloric balance.


RESULTS
Two endocytic receptors, the syndecan-1 heparan sulfate proteoglycan (HSPG) and the LDL receptor, plus one docking receptor, SR-BI, significantly contribute to normal hepatic remnant catabolism. Compelling evidence exists for dysfunction of the syndecan-1 HSPG in diabetic states. The major molecular defect identified so far in poorly controlled type 1 diabetes is impaired hepatic HSPG assembly. In contrast, the primary defect in hepatic HSPGs in type 2 diabetes appears to arise from accelerated de-sulfation, owing to the induction of a sulfatase. Moreover, short-term caloric restriction restores hepatic expression of this sulfatase towards normal.


CONCLUSIONS
Correct identification of hepatic remnant receptors has finally allowed investigations of their molecular dysregulation in diabetes and related conditions. New work points to novel therapeutic targets to correct postprandial dyslipoproteinemia and its consequent arterial damage.
Williams
Kevin Jon
KJ
Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA. kjwilliams@temple.edu
Chen
Keyang
K
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008074:Lipoproteins / Q000737:chemistry / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D019518:Postprandial Period; D011973:Receptors, LDL / Q000378:metabolism
D008074:Lipoproteins; D011973:Receptors, LDL