Key result
ANGPTL4/8 levels were roughly twice as high in type 2 diabetes patients compared to controls and inversely correlated with HDL, with ANGPTL4 acting as a potent endothelial lipase inhibitor.
Why the study?
Because ANGPTL3/8 and ANGPTL4/8 complexes inversely correlate with HDL in control subjects, researchers investigated their levels in type 2 diabetes patients, who can present with decreased HDL.
Observational
Answers are grounded in this paper and cite their sources.
No immediate clinical role for ANGPTL complex measurement; leaves open their contribution to low HDL in T2D.
We previously demonstrated that angiopoietin-like protein 8 (ANGPTL8) forms ANGPTL3/8 and ANGPTL4/8 complexes that increase with feeding to direct fatty acids (FA) toward adipose tissue through differential modulation of lipoprotein lipase (LPL) activity. Each complex correlated inversely with high density lipoprotein cholesterol (HDL) in control subjects. We thus investigated ANGPTL3/8 and ANGPTL4/8 levels in type 2 diabetes patients, who can present with decreased HDL. While ANGPTL3/8 levels in type 2 diabetes patients were similar to those previously observed in normal controls, ANGPTL4/8 levels were roughly twice as high as those in control subjects. Concentrations of ANGPTL3/8 and ANGPTL4/8 in type 2 diabetes patients were inversely correlated with HDL, with the correlation being significant for ANGPTL4/8. We therefore measured the ability of the various ANGPTL proteins and complexes to inhibit endothelial lipase (EL), the enzyme which hydrolyzes phospholipids (PL) in HDL. While confirming ANGPTL3 as an EL inhibitor, we found that ANGPTL4 was a more potent EL inhibitor than ANGPTL3. Interestingly, we observed that while ANGPTL3/8 had increased EL-inhibitory activity compared to ANGPTL3 alone, ANGPTL4/8 exhibited decreased potency in inhibiting EL compared to ANGPTL4 alone. Together, these results show for the first time that ANGPTL4 is a more potent EL inhibitor than ANGPTL3 and suggest a possible reason for why ANGPTL4/8 levels are correlated inversely with HDL.
No takes yet. Share an insight, caveat, or question.
Chen et al. (2021) conducted an observational in Type 2 diabetes. ANGPTL4/8 and ANGPTL3/8 complexes vs. Normal controls was evaluated on HDL levels and endothelial lipase (EL) inhibition. ANGPTL4/8 levels were roughly twice as high in type 2 diabetes patients compared to controls and inversely correlated with HDL, with ANGPTL4 acting as a potent endothelial lipase inhibitor.
Synapse has enriched 10 related papers. Consider them for comparative context: