Apolipoprotein B-48

Nakajima, Katsuyuki; Nagamine, Takahiko; Fujita, Masaki; Ai, Masumi; Tanaka, Akira; Schaefer, Ernst J.

doi:10.1016/b978-0-12-800263-6.00003-3

Cited by 51 publications

(8 citation statements)

References 209 publications

(282 reference statements)

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“…1C). Dietary lipids are absorbed by the apical brush border membrane of enterocytes and metabolized in TG and esterified cholesterol (EC) before storage in cytosolic lipid droplets (LD) or transfer to apolipoprotein B-48 (ApoB-48), which produces chylomicrons (23, 24). Chylomicrons are secreted into the lymph before reaching blood circulation and transport most of diet FA and cholesterol.…”

Section: Resultsmentioning

confidence: 99%

Disentangling Host-Microbiota Regulation of Lipid Secretion by Enterocytes: Insights from Commensals Lactobacillus paracasei and Escherichia coli

Tazi

Araújo

Mulet

et al. 2018

mBio

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The specific contribution of each bacterial species within a complex microbiota to the regulation of host lipid metabolism remains largely unknown. Using two model commensal microorganisms, L. paracasei and E. coli, we demonstrated that both bacterial species impacted host lipid metabolism in a diet-dependent manner and, notably, that L. paracasei-colonized mice but not E. coli-colonized mice resisted high-fat-diet-induced body weight gain. In addition, we set up cellular models of fatty acid absorption and secretion by enterocytes cocultured with bacteria and showed that, in vitro, both L. paracasei and E. coli inhibited lipid secretion, through increased intracellular fat storage and enhanced lipid catabolism, respectively.

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Section: Resultsmentioning

confidence: 99%

Disentangling Host-Microbiota Regulation of Lipid Secretion by Enterocytes: Insights from Commensals Lactobacillus paracasei and Escherichia coli

Tazi

Araújo

Mulet

et al. 2018

mBio

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“…The core of chylomicrons secreted in lymph contains triglycerides and cholesteryl esters. The surface contains phospholipids, unesterified cholesterol, and apolipoproteins such as apoB-48, apoA-I, and apoA-IV [ 24 , 25 ]. The hepatic uptake of cholesterol involves the scavenger receptor class B type I (SR-BI) for high-density lipoprotein (HDL), the low-density lipoprotein (LDL) receptor (LDLR) for LDL, and the chylomicron remnant receptor (CMRR) for chylomicron remnants (CMR).…”

Section: Figurementioning

confidence: 99%

Regulation of Cholesterol Metabolism by Bioactive Components of Soy Proteins: Novel Translational Evidence

Caponio

Wang

Ciaula

et al. 2020

IJMS

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Hypercholesterolemia represents one key pathophysiological factor predisposing to increasing risk of developing cardiovascular disease worldwide. Controlling plasma cholesterol levels and other metabolic risk factors is of paramount importance to prevent the overall burden of disease emerging from cardiovascular-disease-related morbidity and mortality. Dietary cholesterol undergoes micellization and absorption in the small intestine, transport via blood, and uptake in the liver. An important amount of cholesterol originates from hepatic synthesis, and is secreted by the liver into bile together with bile acids (BA) and phospholipids, with all forming micelles and vesicles. In clinical medicine, dietary recommendations play a key role together with pharmacological interventions to counteract the adverse effects of chronic hypercholesterolemia. Bioactive compounds may also be part of initial dietary plans. Specifically, soybean contains proteins and peptides with biological activity on plasma cholesterol levels and this property makes soy proteins a functional food. Here, we discuss how soy proteins modulate lipid metabolism and reduce plasma cholesterol concentrations in humans, with potential outcomes in improving metabolic- and dyslipidemia-related conditions.

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“…In addition, α1PI, apoA1, apoE, HDL, and LDL are produced in the liver. It is thought that apoB100, which incorporates in VLDL, is exclusively synthesized by liver hepatocytes and that apoB48, which incorporates in chylomicrons, is exclusively synthesized by intestinal enterocytes ( Nakajima et al, 2014 ). The effects of Prolastin-C treatment on lipoprotein and apolipoprotein levels in subjects not infected with HIV-1 would be informative in future studies.…”

Section: Discussionmentioning

confidence: 99%

Alphataxin, an Orally Available Small Molecule, Decreases LDL Levels in Mice as a Surrogate for the LDL-Lowering Activity of Alpha-1 Antitrypsin in Humans

Bristow

Winston

2021

Front. Pharmacol.

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The abundant blood protein α1-proteinase inhibitor (α1PI, Αlpha-1, α1-antitrypsin, SerpinA1) is known to bind to the active site of granule-associated human leukocyte elastase (HLE-G). Less well known is that binding of α1PI to cell surface HLE (HLE-CS) induces lymphocyte locomotion mediated by members of the low density lipoprotein receptor family (LDL-RFMs) thereby facilitating low density lipoprotein (LDL) clearance. LDL and α1PI were previously shown to be in negative feedback regulation during transport and clearance of lipoproteins. Further examination herein of the influence of α1PI in lipoprotein regulation using data from a small randomized, double-blind clinical trial shows that treatment of HIV-1-infected individuals with α1PI plasma products lowered apolipoprotein and lipoprotein levels including LDL. Although promising, plasma-purified α1PI is limited in quantity and not a feasible treatment for the vast number of people who need treatment for lowering LDL levels. We sought to develop orally available small molecules to act as surrogates for α1PI. Small molecule β-lactams are highly characterized for their binding to the active site of HLE-G including crystallographic studies at 1.84 Å. Using high throughput screening (HLE-G inhibition, HLE-CS-induced cellular locomotion), we show here that a panel of β-lactams, including the LDL-lowering drug ezetimibe, have the capacity to act as surrogates for α1PI by binding to HLE-G and HLE-CS. Because β-lactams are antibiotics that also have the capacity to promote evolution of antibiotic resistant bacteria, we modified the β-lactam Alphataxin to prevent antibiotic activity. We demonstrate using the diet-induced obesity (DIO) mouse model that Alphataxin, a penam, is as effective in lowering LDL levels as FDA-approved ezetimibe, a monobactam. Non-antibiotic β-lactams provide a promising new therapeutic class of small molecules for lowering LDL levels.

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Apolipoprotein B-48

Cited by 51 publications

References 209 publications

Disentangling Host-Microbiota Regulation of Lipid Secretion by Enterocytes: Insights from Commensals Lactobacillus paracasei and Escherichia coli

Disentangling Host-Microbiota Regulation of Lipid Secretion by Enterocytes: Insights from Commensals Lactobacillus paracasei and Escherichia coli

Regulation of Cholesterol Metabolism by Bioactive Components of Soy Proteins: Novel Translational Evidence

Alphataxin, an Orally Available Small Molecule, Decreases LDL Levels in Mice as a Surrogate for the LDL-Lowering Activity of Alpha-1 Antitrypsin in Humans

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