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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
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. |
format | Online Article Text |
id | pubmed-6600677 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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