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, M Lopez

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)3-21
Number of pages19
JournalCurrent molecular medicine
Volume14
Issue number1
DOIs
Publication statusPublished - Jan 2014

Fingerprint

Sirolimus
Homeostasis
Sensors
Nutrients
Cell signaling
Food
Adipogenesis
Lipogenesis
AMP-Activated Protein Kinases
Ghrelin
Mammals
Protein-Serine-Threonine Kinases
Energy management
Cell growth
Leptin
Metabolic Networks and Pathways
Cell Division
Liver
Cues
Insulin Resistance

Keywords

  • Animals
  • Energy Metabolism
  • Hormones
  • Humans
  • Hypothalamus
  • Models, Biological
  • Multiprotein Complexes
  • Puberty
  • Signal Transduction
  • TOR Serine-Threonine Kinases

Cite this

Martínez de Morentin, P. B., Martinez-Sanchez, N., Roa, J., Ferno, J., Nogueiras, R., Tena-Sempere, M., ... Lopez, M. (2014). Hypothalamic mTOR: the rookie energy sensor. Current molecular medicine, 14(1), 3-21. https://doi.org/10.2174/1566524013666131118103706

Hypothalamic mTOR : the rookie energy sensor. / Martínez de Morentin, P B; Martinez-Sanchez, N; Roa, J; Ferno, J; Nogueiras, R; Tena-Sempere, M; Dieguez, C; Lopez, M.

In: Current molecular medicine, Vol. 14, No. 1, 01.2014, p. 3-21.

Research output: Contribution to journalArticle

Martínez de Morentin, PB, Martinez-Sanchez, N, Roa, J, Ferno, J, Nogueiras, R, Tena-Sempere, M, Dieguez, C & Lopez, M 2014, 'Hypothalamic mTOR: the rookie energy sensor', Current molecular medicine, vol. 14, no. 1, pp. 3-21. https://doi.org/10.2174/1566524013666131118103706
Martínez de Morentin PB, Martinez-Sanchez N, Roa J, Ferno J, Nogueiras R, Tena-Sempere M et al. Hypothalamic mTOR: the rookie energy sensor. Current molecular medicine. 2014 Jan;14(1):3-21. https://doi.org/10.2174/1566524013666131118103706
Martínez de Morentin, P B ; Martinez-Sanchez, N ; Roa, J ; Ferno, J ; Nogueiras, R ; Tena-Sempere, M ; Dieguez, C ; Lopez, M. / Hypothalamic mTOR : the rookie energy sensor. In: Current molecular medicine. 2014 ; Vol. 14, No. 1. pp. 3-21.
@article{a00c2b317f6e4148998612325915d4a0,
title = "Hypothalamic mTOR: the rookie energy sensor",
abstract = "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.",
keywords = "Animals, Energy Metabolism, Hormones, Humans, Hypothalamus, Models, Biological, Multiprotein Complexes, Puberty, Signal Transduction, TOR Serine-Threonine Kinases",
author = "{Mart{\'i}nez de Morentin}, {P B} and N Martinez-Sanchez and J Roa and J Ferno and R Nogueiras and M Tena-Sempere and C Dieguez and M Lopez",
year = "2014",
month = "1",
doi = "10.2174/1566524013666131118103706",
language = "English",
volume = "14",
pages = "3--21",
journal = "Current molecular medicine",
issn = "1566-5240",
publisher = "Bentham Science Publishers B.V.",
number = "1",

}

TY - JOUR

T1 - Hypothalamic mTOR

T2 - the rookie energy sensor

AU - Martínez de Morentin, P B

AU - Martinez-Sanchez, N

AU - Roa, J

AU - Ferno, J

AU - Nogueiras, R

AU - Tena-Sempere, M

AU - Dieguez, C

AU - Lopez, M

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

KW - Animals

KW - Energy Metabolism

KW - Hormones

KW - Humans

KW - Hypothalamus

KW - Models, Biological

KW - Multiprotein Complexes

KW - Puberty

KW - Signal Transduction

KW - TOR Serine-Threonine Kinases

U2 - 10.2174/1566524013666131118103706

DO - 10.2174/1566524013666131118103706

M3 - Article

VL - 14

SP - 3

EP - 21

JO - Current molecular medicine

JF - Current molecular medicine

SN - 1566-5240

IS - 1

ER -