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Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies
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| Zeitschriftentitel: | International Journal of Molecular Sciences |
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| Personen und Körperschaften: | , , , , , , , , |
| In: | International Journal of Molecular Sciences, 20, 2019, 11, S. 2675 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
MDPI AG
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| Schlagwörter: |
| author_facet |
Wilson, Nicholas Steadman, Robert Muller, Ilaria Draman, Mohd Rees, D. Aled Taylor, Peter Dayan, Colin M. Ludgate, Marian Zhang, Lei Wilson, Nicholas Steadman, Robert Muller, Ilaria Draman, Mohd Rees, D. Aled Taylor, Peter Dayan, Colin M. Ludgate, Marian Zhang, Lei |
|---|---|
| author |
Wilson, Nicholas Steadman, Robert Muller, Ilaria Draman, Mohd Rees, D. Aled Taylor, Peter Dayan, Colin M. Ludgate, Marian Zhang, Lei |
| spellingShingle |
Wilson, Nicholas Steadman, Robert Muller, Ilaria Draman, Mohd Rees, D. Aled Taylor, Peter Dayan, Colin M. Ludgate, Marian Zhang, Lei International Journal of Molecular Sciences Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
| author_sort |
wilson, nicholas |
| spelling |
Wilson, Nicholas Steadman, Robert Muller, Ilaria Draman, Mohd Rees, D. Aled Taylor, Peter Dayan, Colin M. Ludgate, Marian Zhang, Lei 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms20112675 <jats:p>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.</jats:p> Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies International Journal of Molecular Sciences |
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| title |
Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies |
| title_unstemmed |
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 |
Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis |
| url |
http://dx.doi.org/10.3390/ijms20112675 |
| publishDate |
2019 |
| physical |
2675 |
| description |
<jats:p>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.</jats:p> |
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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, Wilson, Nicholas, Steadman, Robert, Muller, Ilaria, Draman, Mohd, Rees, D. Aled, Taylor, Peter, Dayan, Colin M., Ludgate, Marian, Zhang, Lei |
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| description | <jats:p>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.</jats:p> |
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| imprint | MDPI AG, 2019 |
| imprint_str_mv | MDPI AG, 2019 |
| institution | DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1 |
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| language | English |
| last_indexed | 2024-03-01T13:35:13.658Z |
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| spelling | Wilson, Nicholas Steadman, Robert Muller, Ilaria Draman, Mohd Rees, D. Aled Taylor, Peter Dayan, Colin M. Ludgate, Marian Zhang, Lei 1422-0067 MDPI AG Inorganic Chemistry Organic Chemistry Physical and Theoretical Chemistry Computer Science Applications Spectroscopy Molecular Biology General Medicine Catalysis http://dx.doi.org/10.3390/ijms20112675 <jats:p>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.</jats:p> Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies International Journal of Molecular Sciences |
| spellingShingle | Wilson, Nicholas, Steadman, Robert, Muller, Ilaria, Draman, Mohd, Rees, D. Aled, Taylor, Peter, Dayan, Colin M., Ludgate, Marian, Zhang, Lei, International Journal of Molecular Sciences, Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies, Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| 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 |
| title_unstemmed | Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies |
| topic | Inorganic Chemistry, Organic Chemistry, Physical and Theoretical Chemistry, Computer Science Applications, Spectroscopy, Molecular Biology, General Medicine, Catalysis |
| url | http://dx.doi.org/10.3390/ijms20112675 |