HDL biology
Lipoprotein-bound free fatty acids drive elevated CETP specific activity in nephrotic syndrome (Arterioscler Thromb Vasc Biol 1997)
Original title: Role of lipoprotein-bound NEFAs in enhancing the specific activity of plasma CETP in the nephrotic syndrome
Plasma CETP activity was significantly higher in 15 patients with untreated idiopathic nephrotic syndrome than in 22 normolipidemic controls (81.5 versus 43.1 micrograms CE/mL/h, P < .001), explained by both higher CETP mass concentration (3.2 versus 2.1 mg/L, P < .001) and higher specific CETP activity (25.3 versus 20.4 micrograms CE/mg/h, P < .05). Elevated CETP activity in nephrotic patients was associated with smaller mean LDL size (24.4 versus 26.3 nm, P < .0001) and reduced HDL2a abundance (29.6% versus 34.8%, P < .05), alongside a marked rise in lipoprotein-bound nonesterified fatty acids (35.4% versus 7.6% of total, P < .01) that increased LDL and HDL electronegative charge. Removing lipoprotein-bound nonesterified fatty acids with fatty acid-poor albumin significantly lowered CETP activity and specific activity in both groups, eliminating the difference in specific CETP activity between nephrotic and control plasma. The authors conclude that lipoprotein-bound nonesterified fatty acids, by increasing lipoprotein electronegative charge, facilitate CETP-mediated lipid transfer in nephrotic syndrome.
Original abstract
Plasma cholesteryl ester transfer protein (CETP) activity, evaluated by the transfer of radiolabeled cholesteryl esters from a tracer dose of tritiated HDL to the plasma apolipoprotein B-containing lipoproteins, was significantly higher in patients with untreated idiopathic nephrotic syndrome (n = 15) than in normolipidemic control subjects (n = 22) (81.5 +/- 8.4 versus 43.1 +/- 3.1 micrograms CE.mL-1.h-1, respectively; P < .001). The increased CETP activity in nephrotic plasma was explained by a significant rise in both the CETP mass concentration (3.2 +/- 0.2 versus 2.1 +/- 0.1 mg/L; P < .001), and the specific CETP activity, calculated as the ratio of CETP activity to CETP mass (25.3 +/- 1.7 versus 20.4 +/- 1.6 micrograms CE.mg-1.h-1; P < .05). Elevated CETP activity in nephrotic patients was shown to be associated with a significant decrease in the mean size of LDL (24.4 +/- 0.5 versus 26.3 +/- 0.5 nm; P < .0001) as well as in the relative abundance of HDL2a (29.6 +/- 1.6% versus 34.8 +/- 1.1%; P < .05). The nephrotic syndrome was characterized by a significant increase in the relative proportion of lipoprotein-bound nonesterified fatty acids (NEFAs) (35.4 +/- 7.7% versus 7.6 +/- 3.0% of total; P < .01), leading to a significant increase in the electronegative charge of LDL (-4.3 +/- 0.1 versus -3.9 +/- 0.1 mV; P < .05) and HDL (-11.5 +/- 0.1 versus -11.1 +/- 0.2 mV; P < .05). Compared with native, non-supplemented plasma, removal of lipoprotein-bound NEFAs by addition of fatty acid-poor albumin to total plasma from nephrotic patients or control subjects significantly decreased CETP activity and specific CETP activity. Specific CETP activity no longer differed between nephrotic and control groups after albumin supplementation (19.7 +/- 1.5 versus 17.7 +/- 1.5 micrograms CE.mg-1.h-1; NS). It is concluded that, in addition to elevated CETP mass concentration, lipoprotein-bound NEFAs, by increasing the negative electrostatic charge of nephrotic lipoproteins, can facilitate the CETP-mediated neutral-lipid transfer reaction in total plasma from nephrotic patients.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.