Butyric Acid Added Apically to Intestinal Caco-2 Cells Elevates Hepatic ApoA-I Transcription and Rescues Lower ApoA-I Expression in Inflamed HepG2 Cells Co-Cultured in the Basolateral Compartment.

Jehad Z Tayyeb,Ronald P Mensink,Jogchum Plat,Herman E Popeijus

doi:10.3390/biom11010071

Jehad Z Tayyeb, Ronald P Mensink + Show 2 more

Open Access

https://doi.org/10.3390/biom11010071

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Journal: Biomolecules	Publication Date: Jan 7, 2021
Citations: 9	License type: CC BY 4.0

Affiliation: Maastricht University, Jeddah University

Abstract

Apolipoprotein A-I (ApoA-I) concentrations are decreased during inflammation, which may reduce high-density lipoprotein (HDL) functionality. Thus, rescuing ApoA-I concentrations during inflammation might help to prevent atherosclerosis. Recent studies have shown that butyric acid (C4) has anti-inflammatory effects and rescues ApoA-I production. However, whether intestinal short chain fatty acids (SCFAs) are able to influence hepatic processes is unknown. Therefore, we investigated C4 anti-inflammatory effects on ApoA-I transcription in the intestine-liver co-culture model. C4 dose-response experiments in the presence or absence of cytokines were performed in a co-culture system including Caco-2 cells, HepG2 cells, or both. Changes in ApoA-I transcription in Caco-2 cells and HepG2 cells were analyzed using qPCR. C4 increased ApoA-I expression in HepG2 cells that cultured alone. When both cells were cultured together, C4 decreased ApoA-I expression in Caco-2 cells and increased ApoA-I expression in HepG2 cells. However, adding C4 to apical Caco-2 cells resulted in a smaller effect in HepG2 cells compared with adding C4 directly to the hepatocytes. Moreover, C4 rescued ApoA-I expression in inflamed HepG2 cells. These findings suggests that intestinal SCFAs can affect hepatic processes. However, the smaller effect in the co-culture experiment indicates cross-talk between intestine and liver.

Highlights

A higher production of short chain fatty acids (SCFAs) in the intestinal lumen may result in various health benefits [1]
To evaluate the effects of C4 on Caco-2 cells (Condition 1, Figure 3A), different doses of C4 were added to the apical surface of the Caco-2 cells on the insert, without HepG2 cells in the lower compartment
When C4 was added to HepG2 cells in the lower compartment without the Caco-2 cells on the insert above (Condition 2, Figure 3B), Apolipoprotein A-I (ApoA-I) mRNA expression dose-dependently increased (p < 0.001), with a maximum of a 4.2-fold at a 6 mM concentration of C4

Summary

Introduction

A higher production of short chain fatty acids (SCFAs) in the intestinal lumen may result in various health benefits [1]. C4 was reduced in intestinal biopsies of Crohn’s disease patients’ mRNA expression and production of pro-inflammatory cytokines, such as TNFα, by the inhibition of nuclear factor kappa B (NF-κB) transactivation [5] Beside these local benefits, SCFAs exert systemically beneficial effects, such as lowering inflammation in macrophages and endothelial cells through the inhibition of inflammatory cytokine production [6] and abating the development of atherosclerosis [7]. SCFAs exert systemically beneficial effects, such as lowering inflammation in macrophages and endothelial cells through the inhibition of inflammatory cytokine production [6] and abating the development of atherosclerosis [7] These latter anti-atherosclerotic effects are thought to be mediated by modulating pro-inflammatory cytokine production, endothelial dysfunction and oxidative stress [8].

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