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Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes

Butyrate is considered the primary energy source of colonocytes and has received wide attention due to its unique health benefits. Insight into the mechanistic effects of butyrate on cellular and metabolic function relies mainly on research in in-vitro-cultured cells. However, cells in culture diffe...

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Autores principales: Bekebrede, Anna F., van Deuren, Thirza, Gerrits, Walter J. J., Keijer, Jaap, de Boer, Vincent C. J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539916/
https://www.ncbi.nlm.nih.gov/pubmed/34681598
http://dx.doi.org/10.3390/ijms222010937
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author Bekebrede, Anna F.
van Deuren, Thirza
Gerrits, Walter J. J.
Keijer, Jaap
de Boer, Vincent C. J.
author_facet Bekebrede, Anna F.
van Deuren, Thirza
Gerrits, Walter J. J.
Keijer, Jaap
de Boer, Vincent C. J.
author_sort Bekebrede, Anna F.
collection PubMed
description Butyrate is considered the primary energy source of colonocytes and has received wide attention due to its unique health benefits. Insight into the mechanistic effects of butyrate on cellular and metabolic function relies mainly on research in in-vitro-cultured cells. However, cells in culture differ from those in vivo in terms of metabolic phenotype and nutrient availability. For translation, it is therefore important to understand the impact of different nutrients on the effects of butyrate. We investigated the metabolic consequences of butyrate exposure under various culturing conditions, with a focus on the interaction between butyrate and glucose. To investigate whether the effects of butyrate were different between cells with high and low mitochondrial capacity, we cultured HT29 cells under either low- (0.5 mM) or high- (25 mM) glucose conditions. Low-glucose culturing increased the mitochondrial capacity of HT29 cells compared to high-glucose (25 mM) cultured HT29 cells. Long-term exposure to butyrate did not alter mitochondrial bioenergetics, but it decreased glycolytic function, regardless of glucose availability. In addition, both high- and low-glucose-grown HT29 cells showed increased lipid droplet accumulation following long-term butyrate exposure. Acute exposure of cultured cells (HT29 and Caco-2) to butyrate increased their oxygen consumption rate (OCR). A simultaneous decrease in extracellular acidification rate (ECAR) was observed. Furthermore, in the absence of glucose, OCR did not increase in response to butyrate. These results lead us to believe that butyrate itself was not responsible for the observed increase in OCR, but, instead, butyrate stimulated pyruvate flux into mitochondria. Indeed, blocking of the mitochondrial pyruvate carrier prevented a butyrate-induced increase in oxygen consumption. Taken together, our results indicate that butyrate itself is not oxidized in cultured cells but instead alters pyruvate flux and induces lipid accumulation.
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spelling pubmed-85399162021-10-24 Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes Bekebrede, Anna F. van Deuren, Thirza Gerrits, Walter J. J. Keijer, Jaap de Boer, Vincent C. J. Int J Mol Sci Article Butyrate is considered the primary energy source of colonocytes and has received wide attention due to its unique health benefits. Insight into the mechanistic effects of butyrate on cellular and metabolic function relies mainly on research in in-vitro-cultured cells. However, cells in culture differ from those in vivo in terms of metabolic phenotype and nutrient availability. For translation, it is therefore important to understand the impact of different nutrients on the effects of butyrate. We investigated the metabolic consequences of butyrate exposure under various culturing conditions, with a focus on the interaction between butyrate and glucose. To investigate whether the effects of butyrate were different between cells with high and low mitochondrial capacity, we cultured HT29 cells under either low- (0.5 mM) or high- (25 mM) glucose conditions. Low-glucose culturing increased the mitochondrial capacity of HT29 cells compared to high-glucose (25 mM) cultured HT29 cells. Long-term exposure to butyrate did not alter mitochondrial bioenergetics, but it decreased glycolytic function, regardless of glucose availability. In addition, both high- and low-glucose-grown HT29 cells showed increased lipid droplet accumulation following long-term butyrate exposure. Acute exposure of cultured cells (HT29 and Caco-2) to butyrate increased their oxygen consumption rate (OCR). A simultaneous decrease in extracellular acidification rate (ECAR) was observed. Furthermore, in the absence of glucose, OCR did not increase in response to butyrate. These results lead us to believe that butyrate itself was not responsible for the observed increase in OCR, but, instead, butyrate stimulated pyruvate flux into mitochondria. Indeed, blocking of the mitochondrial pyruvate carrier prevented a butyrate-induced increase in oxygen consumption. Taken together, our results indicate that butyrate itself is not oxidized in cultured cells but instead alters pyruvate flux and induces lipid accumulation. MDPI 2021-10-10 /pmc/articles/PMC8539916/ /pubmed/34681598 http://dx.doi.org/10.3390/ijms222010937 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bekebrede, Anna F.
van Deuren, Thirza
Gerrits, Walter J. J.
Keijer, Jaap
de Boer, Vincent C. J.
Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes
title Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes
title_full Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes
title_fullStr Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes
title_full_unstemmed Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes
title_short Butyrate Alters Pyruvate Flux and Induces Lipid Accumulation in Cultured Colonocytes
title_sort butyrate alters pyruvate flux and induces lipid accumulation in cultured colonocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8539916/
https://www.ncbi.nlm.nih.gov/pubmed/34681598
http://dx.doi.org/10.3390/ijms222010937
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