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mTOR and regulation of energy homeostasis in humans

Item Type:Review
Title:mTOR and regulation of energy homeostasis in humans
Creators Name:Mannaa, M. and Krämer, S. and Boschmann, M. and Gollasch, M.
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.
Keywords:mTOR, Energy Homeostasis, Obesity, Type-2 Diabetes Mellitus, Eating Behavior, Adipokines, Leptin, Adiponectin, Fibroblast Growth Factor 21 (FGF21), Cholecystokinin (CCK), ADRF, Bone Morphogenic Protein-7 (BMP7), Rapamycin, Everolimus, Animals
Source:Journal of Molecular Medicine
Page Range:1167-1175
Date:October 2013
Official Publication:https://doi.org/10.1007/s00109-013-1057-6
PubMed:View item in PubMed

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