Influence of mTOR in energy and metabolic homeostasis.
Molecular and Cellular Endocrinology. 2014-11-01; 397(1-2): 67-77
DOI: 10.1016/j.mce.2014.07.015
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1. Mol Cell Endocrinol. 2014 Nov;397(1-2):67-77. doi: 10.1016/j.mce.2014.07.015.
Epub 2014 Aug 7.
Influence of mTOR in energy and metabolic homeostasis.
Haissaguerre M(1), Saucisse N(1), Cota D(2).
Author information:
(1)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U862, F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie,
Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.
(2)INSERM, Neurocentre Magendie, Physiopathologie de la Plasticité Neuronale,
U862, F-33000 Bordeaux, France; University of Bordeaux, Neurocentre Magendie,
Physiopathologie de la Plasticité Neuronale, U862, F-33000 Bordeaux, France.
Electronic address: .
The mechanistic (or mammalian) target of rapamycin couples a variety of different
environmental signals, including nutrients and hormones, with the regulation of
several energy-demanding cellular functions, spanning from protein and lipid
synthesis to mitochondrial activity and cytoskeleton dynamics. mTOR forms two
distinct protein complexes in cells, mTORC1 and mTORC2. This review focuses on
recent advances made in understanding the roles played by these two complexes in
the regulation of whole body metabolic homeostasis. Studies carried out in the
past few years have shown that mTORC1 activity in the hypothalamus varies by cell
and stimulus type, and that this complex is critically implicated in the
regulation of food intake and body weight and in the central actions of both
nutrients and hormones, such as leptin, ghrelin and triiodothyronine. As a
regulator of cellular anabolic processes, mTORC1 activity in the periphery favors
adipogenesis, lipogenesis, glucose uptake and beta-cell mass expansion. Much less
is known about the function of mTORC2 in the hypothalamus, while in peripheral
organs this second complex exerts roles strikingly similar to those described for
mTORC1. Deregulation of mTORC1 and mTORC2 is associated with obesity, type 2
diabetes, cancer and neurodegenerative disorders. Insights on the exact
relationship between mTORC1 and mTORC2 in the context of the regulation of
metabolic homeostasis and on the specific molecular mechanisms engaged by these
two complexes in such regulation may provide new avenues for therapy.
Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
DOI: 10.1016/j.mce.2014.07.015
PMID: 25109278 [Indexed for MEDLINE]