Enhanced solubilization and intestinal absorption of cholesterol by oxidized linoleic acid

Abstract

Solubilization of cholesterol in the intestinal lumen by bile acids and the subsequent formation of mixed micelles is an important step in the absorption of cholesterol. We propose that oxidized fatty acids (ox-FA) may mimic bile acids and form mixed micelles with cholesterol much more efficiently, as compared with unoxidized fatty acids, thereby increasing there absorption. In an in vitro assay at concentrations of 1, 5, and 10 mM, oxidized linoleic acid (ox-18:2) increased the solubilization of cholesterol (3.06, 8.16, and 15.46 nmol/ml) in a dose dependent manner compared with a 10 mM unoxidized linoleic acid (unox-18:2 at 0.97 nmol/ml). The uptake of cholesterol solubilized in the presence of ox-18:2 by Caco-2 cells and everted rat intestinal sacs was greater (1.78 and 1.95 nmol/ml respectively) as compared with the cholesterol solubilized in the presence of unox-18:2 (0.29 and 0.61 nmol/ml; P ‫؍‬ 0.05). In addition, when LDL receptor deficient mice were fed a high fat diet along with ox-18:2 their plasma cholesterol levels were greater than animals fed the high fat diet alone (1290 mg/dl vs. 1549 mg/dl, P ‫؍‬ 0.013).From these results, we suggest that ox-FA, by enhancing the solubilization of luminal cholesterol, increases the uptake of cholesterol that might lead to hypercholesterolemia and atherosclerosis.-Penumetcha, M., N. Khan-Merchant, and S. Parthasarathy. Enhanced solubilization and intestinal absorption of cholesterol by oxidized linoleic acid.

High-Fat, Western-Style Diet, Systemic Inflammation, and Gut Microbiota: A Narrative Review

“…This clearly shows that NF-κB stimulation and subsequent pro-inflammatory cytokine production can be caused both by changes in gut flora and HFD, proving convergence in the action of both mechanisms [47,56,137,153,154,180,[229][230][231][232][233]. Neutrophil and macrophage activation is another common aspect of dysbiosis and HFD [28,37,42,48,58,[257][258][259][260][261][262][263][264][265]. An interesting accent of HFD and dysbiosis convergence is related to bile acids, the increased secretion of which can impair gut barrier function and have pro-inflammatory effects [59,241,[253][254][255][256][257], as well as pro-inflammatory effects on the microbiota composition [151,187,[189][190][191].…”

“…Moreover, Caco-2 cells incubation with supra-physiologic hydrophobic BA concentrations enhanced ROS generation in enterocytes resulting in OxS and subsequent aberrations in TJ [255][256][257]. Another mechanism related to BAs by which HFD can modulate intestinal integrity is the structural similarity of LCA and the product of linoleic acid oxidation (13-hydroxyoctadecadienoic acid) [258]. The latter is one of the most abundant SFA in WD.…”

Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review

“…In this setting, PI3K activation promotes intestinal permeability through increased intercellular translocation of the regulatory p85 subunit, enabling PI3K-mediated tyrosine phosphorylation of ZO1 and β catenin, inhibiting structural interactions with OCLN and E-cadherin isomers, respectively (37,38). Last, the oxidation product of a linoleic acid (18:2, n-6), 13-hydroxyoctadecadienoic acid, the most abundant PUFA in a Western-style diet, is at its highest concentration in the intestinal lumen after a fat-rich meal and may promote intestinal permeability similarly to LCA as a result of close structural identity (39).…”

Protection of Lipids from Oxidation by Epicatechin, trans-Resveratrol, and Gallic and Caffeic Acids in Intestinal Model Systems

“…In rats and humans the level of oxidized fatty acids in the serum are proportional to the quantity of oxidized fatty acids in the diet, with increased dietary oxidized fatty acids leading to increased exogenous and endogenous serum oxidized lipoprotein levels (18,19). Others also demonstrated that dietary lipid oxidation products are absorbed in man (20,21). Dietary antioxidants, including plant phenolics, may be of major importance in inhibiting lipid oxidation at those sites where their levels are highest and adverse oxidation occurs, such as in the GIT (4,10).…”

“…In rats and humans the level of oxidized fatty acids in the serum are proportional to the quantity of oxidized fatty acids in the diet, with increased dietary oxidized fatty acids leading to increased exogenous and endogenous serum oxidized lipoprotein levels ( , ). Others also demonstrated that dietary lipid oxidation products are absorbed in man ( , ).…”