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      The Fat Controller: Adipocyte Development

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      PLoS Biology
      Public Library of Science

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          Abstract

          Obesity is a condition characterized by excess adipose tissue that results from positive energy balance and is the most common metabolic disorder in the industrialized world. The obesity epidemic shows no sign of slowing, and it is increasingly a global problem. Serious clinical problems associated with obesity include an increased risk for type 2 diabetes, atherosclerosis, and cancer. Hence, understanding the origin and development of adipocytes and adipose tissue will be critical to the analysis and treatment of metabolic diseases. Historically, albeit incorrectly, adipocytes were thought to be inert cells whose singular function was lipid storage. It is now known that adipocytes have other critical functions; the most important include sensitivity to insulin and the ability to produce and secrete adipocyte-specific endocrine hormones that regulate energy homeostasis in other tissues. Today, adipocytes are recognized as critical regulators of whole-body metabolism and known to be involved in the pathogenesis of a variety of metabolic diseases. All cells come from other cells and many cells arise from precursor cells. Adipocytes are not created from other adipocytes, but they arise from precursor cells. In the last two decades, scientists have discovered the function of many proteins that influence the ability of precursor cells to become adipocytes. If the expansion of the adipose tissue is the problem, it seems logical that adipocyte development inhibitors could be a viable anti-obesity therapeutic. However, factors that block adipocyte development and limit adipocyte expansion also impair metabolic health. This notion may be counterintuitive, but several lines of evidence support the idea that blocking adipocyte development is unhealthy. For this reason it is clear that we need a better understanding of adipocyte development.

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          The distinction of metabolically 'healthy' from 'unhealthy' obese individuals.

          The prevalence and severity of obesity are dramatically increasing throughout the world. Obesity causes a decline in life expectancy due to its associated metabolic and cardiovascular comorbid disorders. Therefore, it will become more important to distinguish obese individuals at high risk for obesity-related metabolic diseases from those who are metabolically 'healthy'. This review focuses on recent evidence suggesting that normal adipose tissue function contributes to the healthy obese phenotype. The majority of individuals with obesity develop insulin resistance, type 2 diabetes, dyslipidemia, gout, hypertension and cardiovascular disease. However, approximately 10-25% of obese individuals are metabolically healthy most likely due to preserved insulin sensitivity. Recent studies suggest that inflammation of visceral adipose tissue, ectopic fat deposition and adipose tissue dysfunction mediate insulin resistance in human obesity independently of total body fat mass. This suggests that mechanisms beyond a positive caloric balance such as inflammation and adipokine release determine the pathological metabolic consequences in patients with obesity. Recommendations for obesity treatment should distinguish the metabolically 'healthy' from 'unhealthy' obese phenotype to identify early the obese person who will benefit the most from losing weight. In addition, novel antiobesity treatment strategies targeting adipose tissue dysfunction are needed.
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            The adipose organ at a glance

            The main parenchymal cells of the adipose organ are adipocytes. White adipocytes store energy, whereas brown adipocytes dissipate energy for thermogenesis. These two cell types with opposing functions can both originate from endothelial cells, and co-exist in the multiple fat depots of the adipose organ – a feature that I propose is crucial for this organ’s plasticity. This poster review provides an overview of the adipose organ, describing its anatomy, cytology, physiological function and histopathology in obesity. It also highlights the remarkable plasticity of the adipose organ, explaining theories of adipocyte transdifferentiation during chronic cold exposure, physical exercise or lactation, as well as in obesity. White-to-brown adipocyte transdifferentiation is of particular medical relevance, because animal data indicate that higher amounts of brown adipose tissue are positively associated with resistance to obesity and its co-morbidities, and that ‘browning’ of the adipose organ curbs these disorders.
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              It's Not How Fat You Are, It's What You Do with It That Counts

              Mechanisms underlying obesity-related metabolic disorders are poorly understood. Samuel Virtue and Antonio Vidal-Puig explore the evidence for an emerging hypothesis that attributes metabolic complications not to obesity per se, but to an individual's capacity for adipose tissue expandability.
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                Author and article information

                Journal
                PLoS Biol
                PLoS Biol
                plos
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, USA )
                1544-9173
                1545-7885
                November 2012
                November 2012
                27 November 2012
                : 10
                : 11
                : e1001436
                Affiliations
                [1]Adipocyte Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, United States of America
                Author notes

                The author has declared that no competing interests exist.

                Article
                PBIOLOGY-D-12-03916
                10.1371/journal.pbio.1001436
                3507952
                23209380
                4667496d-4711-4406-9179-c8f0241a702e
                Copyright @ 2012

                Stephens. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Page count
                Pages: 3
                Funding
                The author received no specific funding for this work.
                Categories
                Primer
                Biology
                Medicine

                Life sciences
                Life sciences

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