Hypothalamic mTOR: The Rookie Energy Sensor
P. B. Martínez de Morentin, N. Martinez-Sanchez, J. Roa, J. Ferno, R. Nogueiras, M. Tena-Sempere, C. Dieguez and M. Lopez
Affiliation: Department of Physiology, School of Medicine-CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela (IDIS), 15782, Spain & CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
Keywords: AMPK, energy balance, energy expenditure, food intake, hypothalamus, mTOR.
Optimal cellular function and therefore organism's survival is determined by the sensitive and
accurate convergence of energy and nutrient abundance to cell growth and division. Among other factors, this
integration is coupled by the target of rapamycin (TOR) pathway, which is able to sense nutrient, energy and
oxygen availability and also growth factor signaling. Indeed, TOR signaling regulates cell energy homeostasis
by coordinating anabolic and catabolic processes for survival. TOR, named mTOR in mammals, is a conserved
serine/threonine kinase that exists in two different complexes, mTORC1 and mTORC2. Recently, studies are
suggesting that alterations of those complexes promote disease and disrupted phenotypes, such as aging,
obesity and related disorders and even cancer. The evidences linking mTOR to energy and metabolic
homeostasis included the following. At central level mTOR regulates food intake and body weight being
involved in the mechanism by which signals such as leptin and ghrelin exert its effects. At peripheral level it
influences adipogenesis and lipogenesis in different tissues including the liver. Noteworthy chronic nutritional
activation of mTOR signaling has been implicated in the development of beta cell mass expansion and on
insulin resistance. Understanding of mTOR and other molecular switches, such as AMP-activated protein
kinase (AMPK), as well as their interrelationship is crucial to know how organisms maintain optimal
homeostasis. This review summarizes the role of hypothalamic TOR complex in cellular energy sensing,
evidenced in the last years, focusing on the metabolic pathways where it is involved and the importance of this
metabolic sensor in cellular and whole body energy management. Understanding the exact role of
hypothalamic mTOR may provide new cues for therapeutic intervention in diseases.
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