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Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies

Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role...

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Autores principales: Wilson, Nicholas, Steadman, Robert, Muller, Ilaria, Draman, Mohd, Rees, D. Aled, Taylor, Peter, Dayan, Colin M., Ludgate, Marian, Zhang, Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600677/
https://www.ncbi.nlm.nih.gov/pubmed/31151314
http://dx.doi.org/10.3390/ijms20112675
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author Wilson, Nicholas
Steadman, Robert
Muller, Ilaria
Draman, Mohd
Rees, D. Aled
Taylor, Peter
Dayan, Colin M.
Ludgate, Marian
Zhang, Lei
author_facet Wilson, Nicholas
Steadman, Robert
Muller, Ilaria
Draman, Mohd
Rees, D. Aled
Taylor, Peter
Dayan, Colin M.
Ludgate, Marian
Zhang, Lei
author_sort Wilson, Nicholas
collection PubMed
description Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have investigated the role of HA in adipogenesis and fat accumulation using human primary subcutaneous preadipocyte/fibroblasts (PFs, n = 12) and subjects of varying body mass index (BMI). The impact of HA on peroxisome proliferator-activated receptor gamma (PPARγ) expression was analysed following siRNA knockdown or HA synthase (HAS)1 and HAS2 overexpression. PFs were cultured in complete or adipogenic medium (ADM) with/without 4-methylumbelliferone (4-MU = HA synthesis inhibitor). Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, and measurement of a terminal differentiation marker. Modulating HA production by HAS2 knockdown or overexpression increased (16%, p < 0.04) or decreased (30%, p = 0.01) PPARγ transcripts respectively. The inhibition of HA by 4-MU significantly enhanced ADM-induced adipogenesis with 1.52 ± 0.18- (ORO), 4.09 ± 0.63- (foci) and 2.6 ± 0.21-(marker)-fold increases compared with the controls, also increased PPARγ protein expression (40%, (p < 0.04)). In human subjects, circulating HA correlated negatively with BMI and triglycerides (r = −0.396 (p = 0.002), r = −0.269 (p = 0.038), respectively), confirming an inhibitory role of HA in human adipogenesis. Thus, enhancing HA action may provide a therapeutic target in obesity.
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spelling pubmed-66006772019-07-16 Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies Wilson, Nicholas Steadman, Robert Muller, Ilaria Draman, Mohd Rees, D. Aled Taylor, Peter Dayan, Colin M. Ludgate, Marian Zhang, Lei Int J Mol Sci Article Hyaluronan (HA), an extra-cellular matrix glycosaminoglycan, may play a role in mesenchymal stem cell differentiation to fat but results using murine models and cell lines are conflicting. Our previous data, illustrating decreased HA production during human adipogenesis, suggested an inhibitory role. We have investigated the role of HA in adipogenesis and fat accumulation using human primary subcutaneous preadipocyte/fibroblasts (PFs, n = 12) and subjects of varying body mass index (BMI). The impact of HA on peroxisome proliferator-activated receptor gamma (PPARγ) expression was analysed following siRNA knockdown or HA synthase (HAS)1 and HAS2 overexpression. PFs were cultured in complete or adipogenic medium (ADM) with/without 4-methylumbelliferone (4-MU = HA synthesis inhibitor). Adipogenesis was evaluated using oil red O (ORO), counting adipogenic foci, and measurement of a terminal differentiation marker. Modulating HA production by HAS2 knockdown or overexpression increased (16%, p < 0.04) or decreased (30%, p = 0.01) PPARγ transcripts respectively. The inhibition of HA by 4-MU significantly enhanced ADM-induced adipogenesis with 1.52 ± 0.18- (ORO), 4.09 ± 0.63- (foci) and 2.6 ± 0.21-(marker)-fold increases compared with the controls, also increased PPARγ protein expression (40%, (p < 0.04)). In human subjects, circulating HA correlated negatively with BMI and triglycerides (r = −0.396 (p = 0.002), r = −0.269 (p = 0.038), respectively), confirming an inhibitory role of HA in human adipogenesis. Thus, enhancing HA action may provide a therapeutic target in obesity. MDPI 2019-05-31 /pmc/articles/PMC6600677/ /pubmed/31151314 http://dx.doi.org/10.3390/ijms20112675 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wilson, Nicholas
Steadman, Robert
Muller, Ilaria
Draman, Mohd
Rees, D. Aled
Taylor, Peter
Dayan, Colin M.
Ludgate, Marian
Zhang, Lei
Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies
title Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies
title_full Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies
title_fullStr Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies
title_full_unstemmed Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies
title_short Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies
title_sort role of hyaluronan in human adipogenesis: evidence from in-vitro and in-vivo studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6600677/
https://www.ncbi.nlm.nih.gov/pubmed/31151314
http://dx.doi.org/10.3390/ijms20112675
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