Adipose mTORC2 is essential for sensory innervation in white adipose tissue and whole-body energy homeostasis

Objective: Adipose tissue, via sympathetic and possibly sensory neurons, communicates with the central nervous system (CNS) to mediate energy homeostasis. In contrast to the sympathetic nervous system, the morphology, role and regulation of the sensory nervous system in adipose tissue are poorly cha...

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Main Authors: Irina C. Frei, Diana Weissenberger, Danilo Ritz, Wolf Heusermann, Marco Colombi, Mitsugu Shimobayashi, Michael N. Hall
Format: Article
Language:English
Published: Elsevier 2022-11-01
Series:Molecular Metabolism
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2212877822001491
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author Irina C. Frei
Diana Weissenberger
Danilo Ritz
Wolf Heusermann
Marco Colombi
Mitsugu Shimobayashi
Michael N. Hall
author_facet Irina C. Frei
Diana Weissenberger
Danilo Ritz
Wolf Heusermann
Marco Colombi
Mitsugu Shimobayashi
Michael N. Hall
author_sort Irina C. Frei
collection DOAJ
description Objective: Adipose tissue, via sympathetic and possibly sensory neurons, communicates with the central nervous system (CNS) to mediate energy homeostasis. In contrast to the sympathetic nervous system, the morphology, role and regulation of the sensory nervous system in adipose tissue are poorly characterized. Methods and results: Taking advantage of recent progress in whole-mount three-dimensional imaging, we identified a network of calcitonin gene-related protein (CGRP)-positive sensory neurons in murine white adipose tissue (WAT). We found that adipose mammalian target of rapamycin complex 2 (mTORC2), a major component of the insulin signaling pathway, is required for arborization of sensory neurons, but not of sympathetic neurons. Time course experiments revealed that adipose mTORC2 is required for maintenance of sensory neurons. Furthermore, loss of sensory innervation in WAT coincided with systemic insulin resistance. Finally, we established that neuronal protein growth-associated protein 43 (GAP43) is a marker for sensory neurons in adipose tissue. Conclusion: Our findings indicate that adipose mTORC2 is necessary for sensory innervation in WAT. In addition, our results suggest that WAT may affect whole-body energy homeostasis via sensory neurons.
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spelling doaj.art-30829a38ac744f36b7edab0306e721a52022-12-22T04:29:24ZengElsevierMolecular Metabolism2212-87782022-11-0165101580Adipose mTORC2 is essential for sensory innervation in white adipose tissue and whole-body energy homeostasisIrina C. Frei0Diana Weissenberger1Danilo Ritz2Wolf Heusermann3Marco Colombi4Mitsugu Shimobayashi5Michael N. Hall6Biozentrum, University of Basel, Basel 4056, SwitzerlandBiozentrum, University of Basel, Basel 4056, SwitzerlandBiozentrum, University of Basel, Basel 4056, SwitzerlandBiozentrum, University of Basel, Basel 4056, SwitzerlandBiozentrum, University of Basel, Basel 4056, SwitzerlandCorresponding author.; Biozentrum, University of Basel, Basel 4056, SwitzerlandCorresponding author.; Biozentrum, University of Basel, Basel 4056, SwitzerlandObjective: Adipose tissue, via sympathetic and possibly sensory neurons, communicates with the central nervous system (CNS) to mediate energy homeostasis. In contrast to the sympathetic nervous system, the morphology, role and regulation of the sensory nervous system in adipose tissue are poorly characterized. Methods and results: Taking advantage of recent progress in whole-mount three-dimensional imaging, we identified a network of calcitonin gene-related protein (CGRP)-positive sensory neurons in murine white adipose tissue (WAT). We found that adipose mammalian target of rapamycin complex 2 (mTORC2), a major component of the insulin signaling pathway, is required for arborization of sensory neurons, but not of sympathetic neurons. Time course experiments revealed that adipose mTORC2 is required for maintenance of sensory neurons. Furthermore, loss of sensory innervation in WAT coincided with systemic insulin resistance. Finally, we established that neuronal protein growth-associated protein 43 (GAP43) is a marker for sensory neurons in adipose tissue. Conclusion: Our findings indicate that adipose mTORC2 is necessary for sensory innervation in WAT. In addition, our results suggest that WAT may affect whole-body energy homeostasis via sensory neurons.http://www.sciencedirect.com/science/article/pii/S2212877822001491Adipose tissueWhole-body energy homeostasismTORC2Sensory nervous systemDiabetesCGRP
spellingShingle Irina C. Frei
Diana Weissenberger
Danilo Ritz
Wolf Heusermann
Marco Colombi
Mitsugu Shimobayashi
Michael N. Hall
Adipose mTORC2 is essential for sensory innervation in white adipose tissue and whole-body energy homeostasis
Molecular Metabolism
Adipose tissue
Whole-body energy homeostasis
mTORC2
Sensory nervous system
Diabetes
CGRP
title Adipose mTORC2 is essential for sensory innervation in white adipose tissue and whole-body energy homeostasis
title_full Adipose mTORC2 is essential for sensory innervation in white adipose tissue and whole-body energy homeostasis
title_fullStr Adipose mTORC2 is essential for sensory innervation in white adipose tissue and whole-body energy homeostasis
title_full_unstemmed Adipose mTORC2 is essential for sensory innervation in white adipose tissue and whole-body energy homeostasis
title_short Adipose mTORC2 is essential for sensory innervation in white adipose tissue and whole-body energy homeostasis
title_sort adipose mtorc2 is essential for sensory innervation in white adipose tissue and whole body energy homeostasis
topic Adipose tissue
Whole-body energy homeostasis
mTORC2
Sensory nervous system
Diabetes
CGRP
url http://www.sciencedirect.com/science/article/pii/S2212877822001491
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