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

1
School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
2
Faculty of Medicine, Universiti Sultan Zainal Abidin, Jalan Sultan Mahmud, Kuala Terengganu 20400, Malaysia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(11), 2675; https://doi.org/10.3390/ijms20112675
Received: 29 April 2019 / Revised: 21 May 2019 / Accepted: 29 May 2019 / Published: 31 May 2019
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism)
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Abstract

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. View Full-Text
Keywords: mesenchymal stem cell; Adipogenesis; fat accumulation; Extracellular matrix; hyaluronan; BMI; 4-methylumbelliferone; PPARγ mesenchymal stem cell; Adipogenesis; fat accumulation; Extracellular matrix; hyaluronan; BMI; 4-methylumbelliferone; PPARγ
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Wilson, N.; Steadman, R.; Muller, I.; Draman, M.; Rees, D.A.; Taylor, P.; Dayan, C.M.; Ludgate, M.; Zhang, L. Role of Hyaluronan in Human Adipogenesis: Evidence from in-Vitro and in-Vivo Studies. Int. J. Mol. Sci. 2019, 20, 2675.

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