Search

Reducing dietary saturated fatty acids (SFA) intake results in a clinically significant lowering of low-density lipoprotein cholesterol (LDL-C) across ethnicities. In contrast, dietary SFA's role in modulating emerging cardiovascular risk factors in different ethnicities remains poorly understood. Elevated levels of lipoprotein(a) [Lp(a)], an independent cardiovascular risk factor, disproportionally affect individuals of African descent. Here, we assessed the responses in Lp(a) levels to dietary SFA reduction in 166 African Americans enrolled in GET-READI (The Gene-Environment Trial on Response in African Americans to Dietary Intervention), a randomized controlled feeding trial. Participants were fed two diets in random order for 5 weeks each: 1) an average American diet (AAD) (37% total fat: 16% SFA), and 2) a diet similar to the Dietary Approaches to Stop Hypertension (DASH) diet (25% total fat: 6% SFA). The participants' mean age was 35 years, 70% were women, the mean BMI was 28 kg/m 2 , and the mean LDL-C was 116 mg/dl. Compared to the AAD diet, LDL-C was reduced by the DASH-type diet (mean change: -12 mg/dl) as were total cholesterol (-16 mg/dl), HDL-C (-5 mg/dl), apoA-1 (-9 mg/dl) and apoB-100 (-5 mg/dl) (all P < 0.0001). In contrast, Lp(a) levels increased following the DASH-type diet compared with AAD (median: 58 vs. 44 mg/dl, P < 0.0001). In conclusion, in a large cohort of African Americans, reductions in SFA intake significantly increased Lp(a) levels while reducing LDL-C. Future studies are warranted to elucidate the mechanism(s) underlying the SFA reduction-induced increase in Lp(a) levels and its role in cardiovascular risk across populations., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Factors influencing the association of apoA-IV with high density lipoproteins (HDL) were investigated by employing a crossed immunoelectrophoresis assay to estimate the distribution of rat plasma apoA-IV between the lipoprotein-free and HDL fractions. Incubation of rat plasma at 37 degrees C resulted in the complete transfer of lipoprotein-free apoA-IV to HDL within 45 min. When plasma obtained from fat-fed rats was incubated at 37 degrees C in the presence of postheparin plasma as a source of lipolytic activity, there was a complete transfer of HDL apoA-IV to the lipoprotein-free fraction within 30 min. With extended incubation (120 min), lipoprotein-free apoA-IV began to transfer back to HDL. Similar patterns of apoA-IV redistribution were seen when plasma from fat-fed rats was incubated with postheparin heart perfusate or was perfused through a beating heart. Incubations conducted with plasma obtained from fasted rats showed similar but markedly attenuated apoA-IV responses. Similar observations were found in vivo following intravenous heparin administration. To determine whether the transfer of apolipoproteins from triglyceride-rich lipoproteins to HDL was partially responsible for the lipolysis-induced redistribution of apoA-IV, purified apoA-I, apoE, and C apolipoproteins were added to plasma from fasted rats. When added to plasma, all of the apolipoproteins tested displaced apoA-IV from HDL in a dose-dependent manner. Conversely, apolipoproteins were removed from HDL by adding Intralipid to plasma from fasted rats. With increasing concentrations of Intralipid, there was a progressive loss of HDL apoC-III and a progressive increase in HDL apoA-IV. Intravenous injection of a bolus of Intralipid to fasted rats resulted in a transient decrease of HDL apoC-III and concomitant increase in HDL apoA-IV. From these studies, we conclude that the binding of apoA-IV to HDL is favored under conditions that result in a relative deficit of HDL surface components, such as following cholesterol esterification by LCAT or transfer of apolipoproteins to nascent triglyceride-rich lipoproteins.