13
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      MiR-130a in the adipogenesis of human SGBS preadipocytes and its susceptibility to androgen regulation

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          ABSTRACT

          Objectives: Adipogenesis is the differentiation process generating mature adipocytes from undifferentiated mesenchymal stem cells. The differentiation can be inhibited by androgens, although knowledge about intracellular effectors of this inhibition is scarce. Recently, androgen-regulated microRNAs were detected as interesting candidates in this context. In this study, we analyse the role of miR-130a and miR-301 in the adipogenesis of human SGBS preadipocytes and whether they are prone to androgen regulation. Materials and Methods: microRNA expression during adipogenic differentiation with or without androgen stimulation was measured by qPCR. Putative target genes of miR-130a and miR-301 were identified by target database search and validated in luciferase reporter assays. Results: miR-130a and miR-301 are both significantly downregulated on day 3 and day 5 of adipogenic differentiation in comparison to day 0. Under androgen stimulation, a significant upregulation of miR-130a was detected after 7 days of adipogenesis lasting to day 14, while miR-301 did not change significantly until day 14. Luciferase reporter assays revealed the androgen receptor (AR), adiponectin (ADIPOQ) and tumour necrosis factor alpha (TNFα) as miR-130a target genes. Conclusions: miR-130a is an androgen-regulated microRNA that is downregulated during the early phase of adipogenesis and exerts its functions by regulating AR and ADIPOQ translation. These data may help to identify new signalling pathways associated with the androgen-mediated inhibition of adipogenesis.

          Related collections

          Most cited references37

          • Record: found
          • Abstract: found
          • Article: not found

          PPARγ and the global map of adipogenesis and beyond.

          Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor (NR) superfamily of ligand-dependent transcription factors (TFs) and function as a master regulator of adipocyte differentiation and metabolism. We review recent breakthroughs in the understanding of PPARγ gene regulation and function in the chromatin context. It is now clear that multiple TFs team up to induce PPARγ during adipogenesis, and that other TFs cooperate with PPARγ to ensure adipocyte-specific genomic binding and function. We discuss how this differs in other PPARγ-expressing cells such as macrophages and how these genome-wide mechanisms are preserved across species despite modest conservation of specific binding sites. These emerging considerations inform our understanding of PPARγ function as well as of adipocyte development and physiology. Published by Elsevier Ltd.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma.

            Obesity has emerged as a global health problem with more than 1.1 billion adults to be classified as overweight or obese, and is associated with type 2 diabetes, cardiovascular disease, and several cancers. Since obesity is characterized by an increased size and/or number of adipocytes, elucidating the molecular events governing adipogenesis is of utmost importance. Recent findings indicate that microRNAs (miRNAs) - small non-protein-coding RNAs that function as post-transcriptional gene regulators - are involved in the regulatory network of adipogenesis. Whereas only a single human miRNA is known so far to be functional in adipogenesis as pro-adipogenic, several mouse miRNAs have been identified very recently as adipogenic regulators, thereby stimulating demand for studying the functional role of miRNAs during adipogenesis in human. Here, we demonstrate that miR-27b abundance decreased during adipogenesis of human multipotent adipose-derived stem (hMADS) cells. Overexpression of miR-27b blunted induction of PPARgamma and C/EBPalpha, two key regulators of adipogenesis, during early onset of adipogenesis and repressed adipogenic marker gene expression and triglyceride accumulation at late stages. PPARgamma has a predicted and highly conserved binding site in its 3'UTR and was indeed confirmed to be a direct target of miR-27b. Thus, these results suggest that the anti-adipogenic effect of miR-27b in hMADS cells is due, at least in part, to suppression of PPARgamma.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway.

              Testosterone supplementation increases skeletal muscle mass and decreases fat mass; however, the underlying mechanisms are unknown. We hypothesized that testosterone regulates body composition by promoting the commitment of mesenchymal pluripotent cells into myogenic lineage and inhibiting their differentiation into adipogenic lineage. Mouse C3H 10T1/2 pluripotent cells were treated with testosterone (0-300 nM) or dihydrotestosterone (DHT, 0-30 nM) for 0-14 d, and myogenic conversion was evaluated by immunocytochemical staining for early (MyoD) and late (myosin heavy chain II; MHC) myogenic markers and by measurements of MyoD and MHC mRNA and protein. Adipogenic differentiation was assessed by adipocyte counting and by measurements of peroxisomal proliferator-activated receptor gamma 2 (PPAR gamma 2) mRNA and PPAR gamma 2 protein and CCAAT/enhancer binding protein alpha. The number of MyoD+ myogenic cells and MHC+ myotubes and MyoD and MHC mRNA and protein levels increased dose dependently in response to testosterone and DHT treatment. Both testosterone and DHT decreased the number of adipocytes and down-regulated the expression of PPAR gamma 2 mRNA and PPAR gamma 2 protein and CCAAT/enhancer binding protein alpha. Androgen receptor mRNA and protein levels were low at baseline but increased after testosterone or DHT treatment. The effects of testosterone and DHT on myogenesis and adipogenesis were blocked by bicalutamide. Therefore, testosterone and DHT regulate lineage determination in mesenchymal pluripotent cells by promoting their commitment to the myogenic lineage and inhibiting their differentiation into the adipogenic lineage through an androgen receptor-mediated pathway. The observation that differentiation of pluripotent cells is androgen dependent provides a unifying explanation for the reciprocal effects of androgens on muscle and fat mass in men.
                Bookmark

                Author and article information

                Journal
                Adipocyte
                Adipocyte
                KADI
                kadi20
                Adipocyte
                Taylor & Francis
                2162-3945
                2162-397X
                2020
                9 April 2020
                9 April 2020
                : 9
                : 1
                : 197-205
                Affiliations
                [a ]Center for Reproductive Medicine and Andrology, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg , Halle, Germany
                [b ]Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics and Adolescent Medicine, Ulm University Medical Center , Ulm, Germany
                Author notes
                CONTACT Hermann M. Behre Hermann.behre@ 123456medizin.uni-halle.de Center for Reproductive Medicine and Andrology, University Hospital Halle (Saale), Martin Luther University Halle-Wittenberg , Ernst-Grube-Str. 40, Halle, Saale 06120, Germany
                [*]

                These authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0002-1888-7813
                Article
                1750256
                10.1080/21623945.2020.1750256
                7153545
                32272867
                7dede2c2-efbb-4671-b81f-9750ac89e087
                © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 January 2020
                : 25 March 2020
                : 26 March 2020
                Page count
                Figures: 5, Tables: 2, References: 44, Pages: 9
                Funding
                Funded by: Deutsche Forschungsgemeinschaft 10.13039/501100001659
                Award ID: GR-4469/1
                This work was supported by the Deutsche Forschungsgemeinschaft [GR-4469/1].
                Categories
                Research Paper

                adipogenesis,androgens,microrna,mir-130a
                adipogenesis, androgens, microrna, mir-130a

                Comments

                Comment on this article