HDL biology
CETP activity differences do not explain how margarine and butter diets change HDL cholesterol (J Lipid Res 2001)
Original title: Impact of hydrogenated fat on high density lipoprotein subfractions and metabolism
Thirty-six subjects (18 women, 18 men) followed three 35-day diets using semiliquid margarine, stick margarine, or butter as the main fat source. LDL-cholesterol rose progressively across the three diets (155, 168, 177 mg/dl), while HDL-cholesterol and apoA-I showed a smaller, non-monotonic pattern (43, 42, 45 mg/dl for HDL-C), driven mainly by changes in apoA-I-only particles (Lp A-I) rather than apoA-I/A-II particles, with little effect on HDL3-cholesterol. CETP activity was measured across the three diets (13.28, 15.74, and 14.35 mmol/h/ml for semiliquid margarine, stick margarine, and butter respectively), but differences in CETP, phospholipid transfer protein activity, or HDL cholesterol esterification rate did not account for the observed HDL-cholesterol differences, pointing instead to the saturated fat content of the diets as the likely driver of the HDL response.
Original abstract
Relative to saturated fatty acids, trans-fatty acids/hydrogenated fat-enriched diets have been reported to increase low density lipoprotein (LDL) cholesterol levels and either decrease or have no effect on high density lipoprotein (HDL) cholesterol levels. To better understand the effect of trans-fatty acids/hydrogenated fat on HDL cholesterol levels and metabolism, 36 subjects (female, n = 18; male, n = 18) were provided with each of three diets containing, as the major sources of fat, vegetable oil-based semiliquid margarine, traditional stick margarine, or butter for 35-day periods. LDL cholesterol levels were 155 +/- 27, 168 +/- 30, and 177 +/- 32 mg/dl after subjects followed the semiliquid margarine, stick margarine, and butter-enriched diets, respectively. HDL cholesterol levels were 43 +/- 10, 42 +/- 9, and 45 +/- 10 mg/dl, respectively. Dietary response in apolipoprotein (apo) A-I levels was similar to that in HDL cholesterol levels. HDL(2) cholesterol levels were 12 +/- 7, 11 +/- 6, and 14 +/- 7 mg/dl, respectively. There was virtually no effect of dietary fat on HDL3 cholesterol levels. The dietary perturbations had a larger effect on particles containing apoA-I only (Lp A-I) than apoA-I and A-II (Lp A-I/A-II). Cholesterol ester transfer protein (CETP) activity was 13.28 +/- 5.76, 15.74 +/- 5.41, and 14.35 +/- 4.77 mmol x h(-1) x ml(-1), respectively. Differences in CETP, phospholipid transfer protein activity, or the fractional esterification rate of cholesterol in HDL did not account for the differences observed in HDL cholesterol levels. These data suggest that the saturated fatty acid component, rather than the trans- or polyunsaturated fatty acid component, of the diets was the putative factor in modulating HDL cholesterol response.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.