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      The Role of Pref-1 during Adipogenic Differentiation: An Overview of Suggested Mechanisms

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          Abstract

          Obesity contributes significantly to the global health burden. A better understanding of adipogenesis, the process of fat formation, may lead to the discovery of novel treatment strategies. However, it is of concern that the regulation of adipocyte differentiation has predominantly been studied using the murine 3T3-L1 preadipocyte cell line and murine experimental animal models. Translation of these findings to the human setting requires confirmation using experimental models of human origin. The ability of mesenchymal stromal/stem cells (MSCs) to differentiate into adipocytes is an attractive model to study adipogenesis in vitro. Differences in the ability of MSCs isolated from different sources to undergo adipogenic differentiation, may be useful in investigating elements responsible for regulating adipogenic differentiation potential. Genes involved may be divided into three broad categories: early, intermediate and late-stage regulators. Preadipocyte factor-1 (Pref-1) is an early negative regulator of adipogenic differentiation. In this review, we briefly discuss the adipogenic differentiation potential of MSCs derived from two different sources, namely adipose-derived stromal/stem cells (ASCs) and Wharton’s Jelly derived stromal/stem cells (WJSCs). We then discuss the function and suggested mechanisms of action of Pref-1 in regulating adipogenesis, as well as current findings regarding Pref-1’s role in human adipogenesis.

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          The canonical Notch signaling pathway: unfolding the activation mechanism.

          Notch signaling regulates many aspects of metazoan development and tissue renewal. Accordingly, the misregulation or loss of Notch signaling underlies a wide range of human disorders, from developmental syndromes to adult-onset diseases and cancer. Notch signaling is remarkably robust in most tissues even though each Notch molecule is irreversibly activated by proteolysis and signals only once without amplification by secondary messenger cascades. In this Review, we highlight recent studies in Notch signaling that reveal new molecular details about the regulation of ligand-mediated receptor activation, receptor proteolysis, and target selection.
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            Economic Burden of Obesity: A Systematic Literature Review

            Background: The rising prevalence of obesity represents an important public health issue. An assessment of its costs may be useful in providing recommendations for policy and decision makers. This systematic review aimed to assess the economic burden of obesity and to identify, measure and describe the different obesity-related diseases included in the selected studies. Methods: A systematic literature search of studies in the English language was carried out in Medline (PubMed) and Web of Science databases to select cost-of-illness studies calculating the cost of obesity in a study population aged ≥18 years with obesity, as defined by a body mass index of ≥30 kg/m², for the whole selected country. The time frame for the analysis was January 2011 to September 2016. Results: The included twenty three studies reported a substantial economic burden of obesity in both developed and developing countries. There was considerable heterogeneity in methodological approaches, target populations, study time frames, and perspectives. This prevents an informative comparison between most of the studies. Specifically, there was great variety in the included obesity-related diseases and complications among the studies. Conclusions: There is an urgent need for public health measures to prevent obesity in order to save societal resources. Moreover, international consensus is required on standardized methods to calculate the cost of obesity to improve homogeneity and comparability. This aspect should also be considered when including obesity-related diseases.
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              Molecular Regulation of Adipogenesis and Potential Anti-Adipogenic Bioactive Molecules

              Adipogenesis is the process by which precursor stem cells differentiate into lipid laden adipocytes. Adipogenesis is regulated by a complex and highly orchestrated gene expression program. In mammalian cells, the peroxisome proliferator-activated receptor γ (PPARγ), and the CCAAT/enhancer binding proteins (C/EBPs) such as C/EBPα, β and δ are considered the key early regulators of adipogenesis, while fatty acid binding protein 4 (FABP4), adiponectin, and fatty acid synthase (FAS) are responsible for the formation of mature adipocytes. Excess accumulation of lipids in the adipose tissue leads to obesity, which is associated with cardiovascular diseases, type II diabetes and other pathologies. Thus, investigating adipose tissue development and the underlying molecular mechanisms is vital to develop therapeutic agents capable of curbing the increasing incidence of obesity and related pathologies. In this review, we address the process of adipogenic differentiation, key transcription factors and proteins involved, adipogenic regulators and potential anti-adipogenic bioactive molecules.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                09 June 2020
                June 2020
                : 21
                : 11
                : 4104
                Affiliations
                [1 ]Institute for Cellular and Molecular Medicine, Department of Immunology, and SAMRC Extramural Unit for Stem Cell Research and Therapy, Faculty of Health Sciences, University of Pretoria, PO Box 2034, Pretoria 0001, South Africa; carinacrdasilva@ 123456gmail.com (C.d.S.); chrisna.durandt@ 123456up.ac.za (C.D.); karlienkallmeyer@ 123456gmail.com (K.K.); melvin.ambele@ 123456up.ac.za (M.A.A.)
                [2 ]Department of Oral Pathology and Oral Biology, School of Dentistry, Faculty of health Sciences, University of Pretoria, PO Box 1266, Pretoria 0001, South Africa
                Author notes
                Author information
                https://orcid.org/0000-0002-5679-4669
                https://orcid.org/0000-0002-9181-694X
                https://orcid.org/0000-0002-6636-2026
                https://orcid.org/0000-0001-6406-2380
                Article
                ijms-21-04104
                10.3390/ijms21114104
                7312882
                32526833
                5dff28b3-344c-4f03-9b63-b0bfba101ea7
                © 2020 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/).

                History
                : 30 April 2020
                : 30 May 2020
                Categories
                Review

                Molecular biology
                adipogenesis,pref-1,adipose-derived stromal/stem cells,wharton’s jelly derived stromal/stem cells,transcription factor,differentiation,notch signaling,mapk kinase signaling

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