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Hypothalamic AMP-activated protein kinase as a mediator of whole body energy balance

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Abstract

The AMP-activated protein kinase (AMPK) is the downstream constituent of a kinase cascade that acts as a sensor of cellular energy levels. Current data unequivocally indicate that hypothalamic AMPK plays a key role in the control of the whole body energy balance, by integrating peripheral signals, such as hormones and metabolites, with central signals, such as neuropeptides, and eliciting allostatic changes in energy homeostasis. Although the molecular details of these interactions are not fully understood, recent evidence has suggested that the interaction between AMPK with hypothalamic lipid metabolism and other metabolic sensors, such as the uncoupling protein 2 (UCP-2), the mammalian target of rapamycin (mTOR) and the deacetylase sirtuin 1 (SIRT1), may play a main role in the hypothalamic control of feeding and energy expenditure. Here, we summarize the role of hypothalamic AMPK as whole body energy gauge. Understanding this key molecule and especially its functions at central level may provide new therapeutic targets for the treatment of metabolic alterations and obesity.

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Acknowledgements

The research leading to these results has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreements n° 245009 (CD and ML) and nº 018734 (AVP), Xunta de Galicia (ML: 10PXIB208164PR), Fondo Investigaciones Sanitarias (ML: PS09/01880), Ministerio de Educacion y Ciencia (CD: BFU2008; ML: RyC-2007-00211), Medical Research Council (AVP), Wellcome Trust (AVP) and United States Public Health Service (AKS: DK-19514 and DK-67509). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII.

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Authors and Affiliations

  1. Department of Physiology, School of Medicine, University of Santiago de Compostela—Instituto de Investigación Sanitaria, Santiago de Compostela, A Coruña, 15782, Spain

    Pablo Blanco Martínez de Morentin, Carmen R. González, Luís Martins, Carlos Diéguez & Miguel López

  2. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, 15706, Spain

    Pablo Blanco Martínez de Morentin, Carmen R. González, Luís Martins, Carlos Diéguez, Manuel Tena-Sempere & Miguel López

  3. Diabetes Research Unit, EBRC-827, Boston Medical Center, Boston, MA, USA

    Asisk K. Saha

  4. Institute of Metabolic Science, Metabolic Research Laboratories, Addenbrooke’s Hospital, University of Cambridge, Cambridge, UK

    Antonio Vidal-Puig

  5. Department of Cell Biology, Physiology and Immunology, University of Córdoba, Córdoba, Spain

    Manuel Tena-Sempere

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  1. Pablo Blanco Martínez de Morentin
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Correspondence to Miguel López.

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Pablo Blanco Martínez de Morentin and Carmen R. González have equally contributed to this work.

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Blanco Martínez de Morentin, P., González, C.R., Saha, A.K. et al. Hypothalamic AMP-activated protein kinase as a mediator of whole body energy balance. Rev Endocr Metab Disord 12, 127–140 (2011). https://doi.org/10.1007/s11154-011-9165-5

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