Purpose of review
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.
Recent findings
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.
Summary
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.
