2 research outputs found
Fatty acid-related modulations of membrane fluidity in cells: detection and implications
Metabolic homeostasis of fatty acids is complex and well-regulated in all organisms. The biosynthesis of saturated fatty acids (SFA) in mammals provides substrates for ?-oxidation and ATP production. Monounsaturated fatty acids (MUFA) are products of desaturases that introduce a methylene group in cis geometry in SFA. Polyunsaturated fatty acids (n-6 and n-3 PUFA) are products of elongation and desaturation of the essential linoleic acid and ?-linolenic acid, respectively. The liver processes dietary fatty acids and exports them in lipoproteins for distribution and storage in peripheral tissues. The three types of fatty acids are integrated in membrane phospholipids and determine their biophysical properties and functions. This study was aimed at investigating effects of fatty acids on membrane biophysical properties under varying nutritional and pathological conditions, by integrating lipidomic analysis of membrane phospholipids with functional two-photon microscopy (fTPM) of cellular membranes. This approach was applied to two case studies: first, pancreatic beta-cells, to investigate hormetic and detrimental effects of lipids. Second, red blood cells extracted from a genetic mouse model defective in lipoproteins, to understand the role of lipids in hepatic diseases and metabolic syndrome and their effect on circulating cells
Distinct Roles of Apolipoproteins A1 and E in the Modulation of High-Density Lipoprotein Composition and Function
In addition to high-density
lipoprotein cholesterol (HDL-C) levels,
HDL quality also appears to be very important for atheroprotection.
Analysis of various clinical paradigms suggests that the lipid and
apolipoprotein composition of HDL defines its size, shape, and functions
and may determine its beneficial effects on human health. Previously,
we reported that like apolipoprotein A-I (Apoa1), apolipoprotein E
(Apoe) is also capable of promoting the <i>de novo</i> biogenesis
of HDL with the participation of ATP binding cassette A lipid transporter
member 1 (Abca1) and plasma enzyme lecithin:cholesterol acyltransferase
(Lcat), in a manner independent of a functional Apoa1. Here, we performed
a comparative analysis of the functions of these HDL subpopulations.
Specifically, Apoe and Apoa1 double-deficient (<i>Apoe</i><sup><i>–/–</i></sup> × <i>Apoa1</i><sup><i>–/–</i></sup>) mice were infected
with <i>APOA1-</i> or <i>APOE3-</i>expressing
adenoviruses, and APOA1-containing HDL (APOA1-HDL) and APOE3-containing
HDL (APOE3-HDL), respectively, were isolated and analyzed by biochemical
and physicochemical methods. Western blot and lipidomic analyses indicated
significant differences in the apolipoprotein and lipid composition
of the two HDL species. Moreover APOE3-HDL presented a markedly reduced
antioxidant potential and Abcg1-mediated cholesterol efflux capacity.
Surprisingly, APOE3-HDL but not APOA1-HDL attenuated LPS-induced production
of TNFα in RAW264.7 cells, suggesting that the anti-inflammatory
effects of APOA1 are dependent on APOE expression. Taken together,
our data indicate that APOA1 and APOE3 recruit different apolipoproteins
and lipids on the HDL particle, leading to structurally and functionally
distinct HDL subpopulations. The distinct role of these two apolipoproteins
in the modulation of HDL functionality may pave the way toward the
development of novel pharmaceuticals that aim to improve HDL functionality