The Plasma Distribution of Non-cholesterol Sterol Precursors and Products of Cholesterol Synthesis and Phytosterols Depend on HDL Concentration.

Valéria Sutti Nunes,Eliton Juniro Da Silva,Eder Carlos Rocha Quintão,Patrícia Miralda Cazita,Eliana Cotta De Faria,Guilherme Da Silva Ferreira,Edna Regina Nakandakare,Vanessa Helena De Souza Zago,Sayonara Ivana Santos De Assis

doi:10.3389/fnut.2022.723555

Abstract

Non-cholesterol sterols are transported in plasma lipoproteins and are consequently important in cholesterol metabolism. We investigated the distribution of non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS), oxysterols, and phytosterols in lipoproteins of healthy subjects differing according to HDL-Cholesterol (HDL-C) plasma levels. Elevated NCSPCS (desmosterol, lathosterol) in the High HDL group suggests that HDL exports these sterols from cells, but not the cholesterol metabolite 24-OHC which was higher in the Low HDL group than in the High HDL group. 27-hydroxycholesterol (27OH-C) plasma levels did not differ between groups. Percentage of NCSPCS and phytosterols predominates in LDL, but did not differ between groups. Thirty percent of desmosterol and lathosterol are present in HDL, with the High HDL group carrying higher percentage of these sterols. A high percentage of campesterol and sitosterol in HDL suggests that phytosterols are absorbed by enterocytes, and that HDL could be a marker of the ABCA1/ApoA1 intestinal activity.

Highlights

Cholesterol synthesis rates like desmosterol, lathosterol, and squalene represent non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS) that are carried by lipoproteins
Triglycerides and very-low-density lipoproteins (VLDL)-C plasma levels were lower in the High high-density lipoproteins (HDL) group when compared to the Low HDL and Control groups
The concentration of 24-OHC is higher in the Low HDL group (p = 0.024) when compared to High HDL participants but the percentage distribution in lipoproteins did not differ between groups (Table 2)

Summary

Introduction

Cholesterol synthesis rates like desmosterol, lathosterol, and squalene represent non-cholesterol sterol precursors of cholesterol synthesis (NCSPCS) that are carried by lipoproteins. Individuals with elevated high-density lipoprotein cholesterol (HDL-C) plasma levels have greater plasma concentrations of cholesterol absorption markers (campesterol and sitosterol) and lower plasma concentration of lathosterol which is a marker of body cholesterol synthesis [4]. 7α-Hydroxycholesterol (7-OH-C) is formed from cholesterol by CYP7A1 and represents the first. Sterol Distribution in Lipoproteins metabolite in the neutral pathway of bile acid biosynthesis [6, 7]. 27-hydroxycholesterol (27-OHC), and 3β-hydroxycholest-5-en(25R)26-oic acid (3β-HCA) are both formed from cholesterol by CYP27A1 and are the first members of the acidic, or alternative, pathway of bile acid biosynthesis [6, 8]. Oxysterols are more than simple metabolites in the pathway from cholesterol to bile acids having anti-atherosclerotic activity by eliminating excess cell cholesterol through the ATP Binding Cassette Subfamily A Member 1 (ABCA1) [11], or by passive diffusion. As mandatory components that mediate cholesterol excretion, 24-hydroxycholesterol (24-OHC) and 27-hydroxycholesterol (27-OHC) are important molecules in maintaining body cholesterol homeostasis

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