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Int. J. Mol. Sci. 2018, 19(9), 2622; https://doi.org/10.3390/ijms19092622

p53 Functions in Adipose Tissue Metabolism and Homeostasis

1
Gottfried Schatz Research Center for Cell Signaling, Metabolism & Aging, Department of Cell Biology, Histology and Embryology, Medical University Graz, 8010 Graz, Austria
2
Berlin Institute of Health, Institute of Pharmacology, Center for Cardiovascular Research, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 10117 Berlin, Germany
3
Department of Adipocyte Development and Nutrition, German Institute of Human Nutrition, 14558 Potsdam, Germany
4
German Center for Diabetes Research (DZD), München-Neuherberg, 85764 Neuherberg, Germany
5
Institute of Nutritional Science, University of Potsdam, Potsdam-Nuthetal, 14558 Nuthetal, Germany
6
BioTechMed-Graz, 8010 Graz, Austria
*
Author to whom correspondence should be addressed.
Received: 31 July 2018 / Revised: 24 August 2018 / Accepted: 30 August 2018 / Published: 4 September 2018
(This article belongs to the Special Issue Nutrition, Brown and White Adipose Tissue)
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Abstract

As a tumor suppressor and the most frequently mutated gene in cancer, p53 is among the best-described molecules in medical research. As cancer is in most cases an age-related disease, it seems paradoxical that p53 is so strongly conserved from early multicellular organisms to humans. A function not directly related to tumor suppression, such as the regulation of metabolism in nontransformed cells, could explain this selective pressure. While this role of p53 in cellular metabolism is gradually emerging, it is imperative to dissect the tissue- and cell-specific actions of p53 and its downstream signaling pathways. In this review, we focus on studies reporting p53’s impact on adipocyte development, function, and maintenance, as well as the causes and consequences of altered p53 levels in white and brown adipose tissue (AT) with respect to systemic energy homeostasis. While whole body p53 knockout mice gain less weight and fat mass under a high-fat diet owing to increased energy expenditure, modifying p53 expression specifically in adipocytes yields more refined insights: (1) p53 is a negative regulator of in vitro adipogenesis; (2) p53 levels in white AT are increased in diet-induced and genetic obesity mouse models and in obese humans; (3) functionally, elevated p53 in white AT increases senescence and chronic inflammation, aggravating systemic insulin resistance; (4) p53 is not required for normal development of brown AT; and (5) when p53 is activated in brown AT in mice fed a high-fat diet, it increases brown AT temperature and brown AT marker gene expression, thereby contributing to reduced fat mass accumulation. In addition, p53 is increasingly being recognized as crucial player in nutrient sensing pathways. Hence, despite existence of contradictory findings and a varying density of evidence, several functions of p53 in adipocytes and ATs have been emerging, positioning p53 as an essential regulatory hub in ATs. Future studies need to make use of more sophisticated in vivo model systems and should identify an AT-specific set of p53 target genes and downstream pathways upon different (nutrient) challenges to identify novel therapeutic targets to curb metabolic diseases. View Full-Text
Keywords: p53; adipose tissue; metabolic syndrome; obesity; adipogenesis; insulin resistance p53; adipose tissue; metabolic syndrome; obesity; adipogenesis; insulin resistance
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Krstic, J.; Reinisch, I.; Schupp, M.; Schulz, T.J.; Prokesch, A. p53 Functions in Adipose Tissue Metabolism and Homeostasis. Int. J. Mol. Sci. 2018, 19, 2622.

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