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- Author: Antonio Vidal-Puig x
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Wellcome Trust Sanger Institute, Metabolic Research Laboratories, Wellcome Trust Genome Campus, Hinxton, UK
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Wellcome Trust Sanger Institute, Metabolic Research Laboratories, Wellcome Trust Genome Campus, Hinxton, UK
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Confirmation of the presence of functional brown adipose tissue (BAT) in humans has renewed interest in investigating the potential therapeutic use of this tissue. The finding that its activity positively correlates with decreased BMI, decreased fat content, and augmented energy expenditure suggests that increasing BAT mass/activity or browning of white adipose tissue (WAT) could be a strategy to prevent or treat obesity and its associated morbidities. The challenge now is to find a safe and efficient way to develop this idea. Whereas BAT has being widely studied in murine models both in vivo and in vitro, there is an urgent need for human cellular models to investigate BAT physiology and functionality from a molecular point of view. In this review, we focus on the latest insights surrounding BAT development and activation in rodents and humans. Then, we discuss how the availability of murine models has been essential to identify BAT progenitors and trace their lineage. Finally, we address how this information can be exploited to develop human cellular models for BAT differentiation/activation. In this context, human embryonic stem and induced pluripotent stem cells-based cellular models represent a resource of great potential value, as they can provide a virtually inexhaustible supply of starting material for functional genetic studies, -omics based analysis and validation of therapeutic approaches. Moreover, these cells can be readily genetically engineered, opening the possibility of generating patient-specific cellular models, allowing the investigation of the influence of different genetic backgrounds on BAT differentiation in pathological or in physiological states.
Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Department of Medicine, Endocrine Department, Metabolic Research Laboratories, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña) 15782, Spain
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Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Department of Medicine, Endocrine Department, Metabolic Research Laboratories, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña) 15782, Spain
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Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Department of Medicine, Endocrine Department, Metabolic Research Laboratories, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña) 15782, Spain
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Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Department of Medicine, Endocrine Department, Metabolic Research Laboratories, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña) 15782, Spain
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Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Department of Medicine, Endocrine Department, Metabolic Research Laboratories, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña) 15782, Spain
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Department of Physiology, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Department of Medicine, Endocrine Department, Metabolic Research Laboratories, School of Medicine, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (A Coruña) 15782, Spain
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Ghrelin, the endogenous ligand of the GH secretagogue receptor, has a pleiotropic role in the modulation of energy balance. Recent evidence has demonstrated that besides its orexigenic role, ghrelin regulates central and peripheral lipid metabolism through specific control of hypothalamic AMP-activated protein kinase (AMPK), a critical metabolic gauge regulating both cellular and whole-body energy homeostasis. In this review, we summarize the new milestones of ghrelin's actions on energy balance, with particular focus on its molecular interaction with hypothalamic AMPK and fatty acid metabolism. Understanding this new metabolic pathway can provide new therapeutic targets for the treatment of obesity and the metabolic syndrome.
