4.8 Article

The role of somatosensory innervation of adipose tissues

Journal

NATURE
Volume 609, Issue 7927, Pages 569-+

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41586-022-05137-7

Keywords

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Funding

  1. Howard Hughes Medical Institute
  2. NIH [R35 NS105067, R01AT012051]
  3. NIH Director's New Innovator Award [DP2DK128800]
  4. NIDDK [K01DK114165]
  5. Whitehall Foundation
  6. Baxter Foundation
  7. Dorris Scholars fellowship
  8. Damon Runyon Cancer Research Foundation [DRG-2405-20]
  9. Fundacion Alfonso Martin Escudero postdoctoral fellowship

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Adipose tissues are regulated by sensory neurons from the dorsal root ganglia, which modulate adipocyte function and energy metabolism through their communication with the central nervous system.
Adipose tissues communicate with the central nervous system to maintain whole-body energy homeostasis. The mainstream view is that circulating hormones secreted by the fat convey the metabolic state to the brain, which integrates peripheral information and regulates adipocyte function through noradrenergic sympathetic output(1). Moreover, somatosensory neurons of the dorsal root ganglia innervate adipose tissue(2). However, the lack of genetic tools to selectively target these neurons has limited understanding of their physiological importance. Here we developed viral, genetic and imaging strategies to manipulate sensory nerves in an organ-specific manner in mice. This enabled us to visualize the entire axonal projection of dorsal root ganglia from the soma to subcutaneous adipocytes, establishing the anatomical underpinnings of adipose sensory innervation. Functionally, selective sensory ablation in adipose tissue enhanced the lipogenic and thermogenetic transcriptional programs, resulting in an enlarged fat pad, enrichment of beige adipocytes and elevated body temperature under thermoneutral conditions. The sensory-ablation-induced phenotypes required intact sympathetic function. We postulate that beige-fat-innervating sensory neurons modulate adipocyte function by acting as a brake on the sympathetic system. These results reveal an important role of the innervation by dorsal root ganglia of adipose tissues, and could enable future studies to examine the role of sensory innervation of disparate interoceptive systems.

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