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mTOR and regulation of energy homeostasis in humans

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Abstract

Patients treated with the mammalian or mechanistic target of rapamycin (mTOR) inhibitor everolimus in order to slow progression of autosomal-dominant polycystic kidney disease (ADPKD) showed a significant reduction of body weight. Although the detailed mechanism of how mTOR inhibition interferes with body weight regulation is rather unclear, present data suggest that this effect is mediated by both central and peripheral mechanisms. These findings in ADPKD patients are in contrast to well-documented effects of hypothalamic mTOR on regulation of energy homeostasis and eating behavior in rodents. In a number of rodent models, the mTOR inhibitor rapamycin induces increased food intake, which is accompanied by increased body weight. However, animal data are inconsistent. This review highlights some of the regulatory signals and key mechanisms that are important for balancing energy intake and energy expenditure with a special focus on adipose tissue-derived adipokines and their interaction with mTOR regarding local regulation of tissue perfusion and metabolism and overall systemic energy homeostasis. Specifically, clinical aspects of an impaired mTOR signaling pathway regarding the development of obesity and type-2 diabetes mellitus will be discussed.

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  1. Mammalian or mechanistic target of rapamycin

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Authors and Affiliations

  1. Campus Virchow Klinikum, Medical Department, Division of Nephrology and Medical Intensive Care Medicine, Charité—Universitätsmedizin Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Marwan Mannaa & Maik Gollasch

  2. Experimental and Clinical Research Center (ECRC)—a joint co-operation between Charité—Universitätsmedizin Berlin and Max-Delbrück-Center for Molecular Medicine, Berlin, Germany

    Marwan Mannaa, Michael Boschmann & Maik Gollasch

  3. German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Nuthetal, Germany

    Marwan Mannaa & Stephanie Krämer

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  1. Marwan Mannaa
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Correspondence to Marwan Mannaa or Maik Gollasch.

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Mannaa, M., Krämer, S., Boschmann, M. et al. mTOR and regulation of energy homeostasis in humans. J Mol Med 91, 1167–1175 (2013). https://doi.org/10.1007/s00109-013-1057-6

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  • DOI: https://doi.org/10.1007/s00109-013-1057-6

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