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      Region‐specific effects of oestradiol on adipose‐derived stem cell differentiation in post‐menopausal women

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          Abstract

          The goal of this study was to determine the effect of acute transdermal 17β‐oestradiol (E 2) on the adipogenic potential of subcutaneous adipose‐derived stem cells ( ASC) in post‐menopausal women. Post‐menopausal women ( n = 11; mean age 57 ± 4.5 years) were treated for 2 weeks, in a randomized, cross‐over design, with transdermal E 2 (0.15 mg) or placebo patches. Biopsies of abdominal ( AB) and femoral ( FEM) subcutaneous adipose tissue ( SAT) were obtained after each treatment and mature adipocytes were analysed for cell size and ASC for their capacity for proliferation (growth rate), differentiation (triglyceride accumulation) and susceptibility to tumour necrosis factor alpha‐induced apoptosis. Gene expression of oestrogen receptors α and β ( ESR1 and ESR2), perilipin 1 and hormone‐sensitive lipase ( HSL), was also assessed. In FEM SAT, but not AB SAT, 2 weeks of E 2 significantly ( P = 0.03) increased ASC differentiation and whole SAT HSL mRNA expression ( P = 0.03) compared to placebo. These changes were not associated with mRNA expression of oestrogen receptors α and β, but HSL expression was significantly increased in FEM SAT with transdermal E 2 treatment. Adipose‐derived stem cells proliferation and apoptosis did not change in either SAT depot after E 2 compared with placebo. Short‐term E 2 appeared to increase the adipogenic potential of FEM, but not AB, SAT in post‐menopausal women with possible implications for metabolic disease. Future studies are needed to determine longer term impact of E 2 on regional SAT accumulation in the context of positive energy imbalance.

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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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            Adipose tissue expandability, lipotoxicity and the Metabolic Syndrome--an allostatic perspective.

            While the link between obesity and type 2 diabetes is clear on an epidemiological level, the underlying mechanism linking these two common disorders is not as clearly understood. One hypothesis linking obesity to type 2 diabetes is the adipose tissue expandability hypothesis. The adipose tissue expandability hypothesis states that a failure in the capacity for adipose tissue expansion, rather than obesity per se is the key factor linking positive energy balance and type 2 diabetes. All individuals possess a maximum capacity for adipose expansion which is determined by both genetic and environmental factors. Once the adipose tissue expansion limit is reached, adipose tissue ceases to store energy efficiently and lipids begin to accumulate in other tissues. Ectopic lipid accumulation in non-adipocyte cells causes lipotoxic insults including insulin resistance, apoptosis and inflammation. This article discusses the links between adipokines, inflammation, adipose tissue expandability and lipotoxicity. Finally, we will discuss how considering the concept of allostasis may enable a better understanding of how diabetes develops and allow the rational design of new anti diabetic treatments. Copyright (c) 2009 Elsevier B.V. All rights reserved.
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              Adipocyte Turnover: Relevance to Human Adipose Tissue Morphology

              OBJECTIVE Adipose tissue may contain few large adipocytes (hypertrophy) or many small adipocytes (hyperplasia). We investigated factors of putative importance for adipose tissue morphology. RESEARCH DESIGN AND METHODS Subcutaneous adipocyte size and total fat mass were compared in 764 subjects with BMI 18–60 kg/m2. A morphology value was defined as the difference between the measured adipocyte volume and the expected volume given by a curved-line fit for a given body fat mass and was related to insulin values. In 35 subjects, in vivo adipocyte turnover was measured by exploiting incorporation of atmospheric 14C into DNA. RESULTS Occurrence of hyperplasia (negative morphology value) or hypertrophy (positive morphology value) was independent of sex and body weight but correlated with fasting plasma insulin levels and insulin sensitivity, independent of adipocyte volume (β-coefficient = 0.3, P < 0.0001). Total adipocyte number and morphology were negatively related (r = −0.66); i.e., the total adipocyte number was greatest in pronounced hyperplasia and smallest in pronounced hypertrophy. The absolute number of new adipocytes generated each year was 70% lower (P < 0.001) in hypertrophy than in hyperplasia, and individual values for adipocyte generation and morphology were strongly related (r = 0.7, P < 0.001). The relative death rate (∼10% per year) or mean age of adipocytes (∼10 years) was not correlated with morphology. CONCLUSIONS Adipose tissue morphology correlates with insulin measures and is linked to the total adipocyte number independently of sex and body fat level. Low generation rates of adipocytes associate with adipose tissue hypertrophy, whereas high generation rates associate with adipose hyperplasia.
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                Author and article information

                Contributors
                rachael.vanpelt@ucdenver.edu
                Journal
                J Cell Mol Med
                J. Cell. Mol. Med
                10.1111/(ISSN)1582-4934
                JCMM
                Journal of Cellular and Molecular Medicine
                John Wiley and Sons Inc. (Hoboken )
                1582-1838
                1582-4934
                15 November 2016
                April 2017
                : 21
                : 4 ( doiID: 10.1111/jcmm.2017.21.issue-4 )
                : 677-684
                Affiliations
                [ 1 ] Department of NutritionColorado State University Fort Collins COUSA
                [ 2 ] Department of Medicine Division of Geriatric MedicineUniversity of Colorado Anschutz Medical Campus Aurora COUSA
                [ 3 ] Department of Medicine Division of Endocrinology, Metabolism and DiabetesUniversity of Colorado Anschutz Medical Campus Aurora COUSA
                [ 4 ]Denver Health and Hospital Authority Denver COUSA
                Author notes
                [*] [* ] Correspondence to: Rachael E. VAN PELT, Ph.D.

                E‐mail: rachael.vanpelt@ 123456ucdenver.edu

                Article
                JCMM13011
                10.1111/jcmm.13011
                5345675
                27862950
                48595385-73fd-4204-b12f-a3a8c3636671
                © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 July 2016
                : 18 September 2016
                Page count
                Figures: 4, Tables: 2, Pages: 8, Words: 5966
                Funding
                Funded by: National Institutes of Health
                Award ID: R01 DK077992
                Award ID: R01 DK088105
                Award ID: T32 AG000279
                Award ID: P50 HD073063
                Award ID: P30 DK048520
                Award ID: UL1 TR000154
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                jcmm13011
                April 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.8 mode:remove_FC converted:10.03.2017

                Molecular medicine
                adipose tissue,oestrogen,stem cells,menopause,adipogenesis
                Molecular medicine
                adipose tissue, oestrogen, stem cells, menopause, adipogenesis

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