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

Adipose tissue, via sympathetic and 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 is poorly characterized. Taking ad...

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Bibliographic Details
Published inbioRxiv
Main Authors Frei, Irina C, Weissenberger, Diana, Ritz, Danilo, Wolf Heusermann, Colombi, Marco, Shimobayashi, Mitsugu, Hall, Michael N
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 22.03.2022
Subjects
Adipose tissue
Body fat
Calcitonin
Calcitonin gene-related peptide
Central nervous system
Energy balance
Homeostasis
Innervation
Insulin
Insulin resistance
Nervous system
Neural networks
Rapamycin
Sensory neurons
Signal transduction
Sympathetic nerves
Sympathetic nervous system
TOR protein
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Summary:Adipose tissue, via sympathetic and 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 is poorly characterized. Taking advantage of recent progress in whole-mount three-dimensional imaging of adipose tissue, we identified a neuronal network of calcitonin gene-related protein (CGRP)-positive sensory neurons in white adipose tissue (WAT). Furthermore, we show that adipose mammalian target of rapamycin complex 2 (mTORC2), a major component of the insulin signaling pathway, mediates sensory innervation in WAT. Based on visualization of neuronal networks, mTORC2-deficient WAT displayed reduced arborization of (CGRP)-positive sensory neurons, while sympathetic neurons were unaffected. This selective loss of sensory innervation followed reduced expression of growth-associated protein 43 (GAP43) in CGRP-positive sensory neurons. Finally, we found that loss of sensory innervation in WAT correlated with systemic insulin resistance. Our findings suggest that adipose mTORC2 is necessary for sensory innervation in WAT which likely contributes to WAT-to-CNS communication. Competing Interest Statement The authors have declared no competing interest.
DOI:10.1101/2022.03.21.485116