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      Two Faces of White Adipose Tissue with Heterogeneous Adipogenic Progenitors

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          Abstract

          Chronic energy surplus increases body fat, leading to obesity. Since obesity is closely associated with most metabolic complications, pathophysiological roles of adipose tissue in obesity have been intensively studied. White adipose tissue is largely divided into subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT). These two white adipose tissues are similar in their appearance and lipid storage functions. Nonetheless, emerging evidence has suggested that SAT and VAT have different characteristics and functional roles in metabolic regulation. It is likely that there are intrinsic differences between VAT and SAT. In diet-induced obese animal models, it has been reported that adipogenic progenitors in VAT rapidly proliferate and differentiate into adipocytes. In obesity, VAT exhibits elevated inflammatory responses, which are less prevalent in SAT. On the other hand, SAT has metabolically beneficial effects. In this review, we introduce recent studies that focus on cellular and molecular components modulating adipogenesis and immune responses in SAT and VAT. Given that these two fat depots show different functions and characteristics depending on the nutritional status, it is feasible to postulate that SAT and VAT have different developmental origins with distinct adipogenic progenitors, which would be a key determining factor for the response and accommodation to metabolic input for energy homeostasis.

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          Most cited references47

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          Developmental origin of fat: tracking obesity to its source.

          The development of obesity not only depends on the balance between food intake and caloric utilization but also on the balance between white adipose tissue, which is the primary site of energy storage, and brown adipose tissue, which is specialized for energy expenditure. In addition, some sites of white fat storage in the body are more closely linked than others to the metabolic complications of obesity, such as diabetes. In this Review, we consider how the developmental origins of fat contribute to its physiological, cellular, and molecular heterogeneity and explore how these factors may play a role in the growing epidemic of obesity.
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            Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI.

            Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating "adipose tissue fibrosis" as a hallmark of metabolically challenged adipocytes. Collagen VI is a highly enriched extracellular matrix component of adipose tissue. The absence of collagen VI results in the uninhibited expansion of individual adipocytes and is paradoxically associated with substantial improvements in whole-body energy homeostasis, both with high-fat diet exposure and in the ob/ob background. Collectively, our data suggest that weakening the extracellular scaffold of adipocytes enables their stress-free expansion during states of positive energy balance, which is consequently associated with an improved inflammatory profile. Therefore, the disproportionate accumulation of extracellular matrix components in adipose tissue may not be merely an epiphenomenon of metabolically challenging conditions but may also directly contribute to a failure to expand adipose tissue mass during states of excess caloric intake.
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              Fibrosis and adipose tissue dysfunction.

              Fibrosis is increasingly appreciated as a major player in adipose tissue dysfunction. In rapidly expanding adipose tissue, pervasive hypoxia leads to an induction of HIF1α that in turn leads to a potent profibrotic transcriptional program. The pathophysiological impact of adipose tissue fibrosis is likely to play an equally important role on systemic metabolic alterations as fibrotic conditions play in the liver, heart, and kidney. Here, we discuss recent advances in our understanding of the genesis, modulation, and systemic impact of excessive extracellular matrix (ECM) accumulation in adipose tissue of both rodents and humans and the ensuing impact on metabolic dysfunction. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Diabetes Metab J
                Diabetes Metab J
                DMJ
                Diabetes & Metabolism Journal
                Korean Diabetes Association
                2233-6079
                2233-6087
                December 2019
                26 December 2019
                : 43
                : 6
                : 752-762
                Affiliations
                National Creative Research Initiatives Center for Adipose Tissue Remodeling, Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, Seoul, Korea.
                Author notes
                Corresponding author: Jae Bum Kim. Institute of Molecular Biology and Genetics, Department of Biological Sciences, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea. jaebkim@ 123456snu.ac.kr
                Author information
                https://orcid.org/0000-0003-1130-1231
                https://orcid.org/0000-0003-2337-6935
                Article
                10.4093/dmj.2019.0174
                6943255
                31902145
                770bc921-2956-4be7-a25f-4d60e8f64403
                Copyright © 2019 Korean Diabetes Association

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

                History
                : 20 September 2019
                : 28 October 2019
                Funding
                Funded by: Ministry of Science, ICT and Future Planning, CrossRef https://doi.org/10.13039/501100003621;
                Award ID: 2011-0018312
                Funded by: BK21;
                Categories
                Review
                Obesity and Metabolic Syndrome

                Endocrinology & Diabetes
                adipogenesis,adipose tissue,energy metabolism,inflammation,obesity,stem cells
                Endocrinology & Diabetes
                adipogenesis, adipose tissue, energy metabolism, inflammation, obesity, stem cells

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