Abstract
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 output1. Moreover, somatosensory neurons of the dorsal root ganglia innervate adipose tissue2. 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 569-574 |
| Number of pages | 6 |
| Journal | Nature |
| Volume | 609 |
| Issue number | 7927 |
| DOIs | |
| State | Published - Sep 15 2022 |
Funding
We thank E. Saez, P. Cohen, C.-H. Lee, K. L. Marshall and I. Daou for their input; B. E. Deverman for advice with AAV vector engineering; K. Deisseroth, D. Gibbs and C. Ramakrishnan for the mScarlet and sfGFP plasmids; J. Stirman and K. Spencer for the imaging support; the staff at Scripps genomics core and Sanford Burnham Prebys histology core for sample preparation; A. Chesler and R. Z. Hill for their feedback on manuscript; and all members of the Ye laboratory, Patapoutian laboratory and Dorris Neuroscience Center for their support and feedback. This work was supported by the Howard Hughes Medical Institute; NIH grants R35 NS105067 and R01AT012051 (to A.P.); NIH Director’s New Innovator Award DP2DK128800 (to L.Y.), NIDDK K01DK114165 (to L.Y.), Whitehall Foundation (to L.Y.) and Baxter Foundation (to L.Y.); Y.W. was supported by the Dorris Scholars fellowship. Y.Z. is a Merck Fellow of the Damon Runyon Cancer Research Foundation, DRG-2405-20. M.D.M.-G. was supported by the Fundacion Alfonso Martin Escudero postdoctoral fellowship. We thank E. Saez, P. Cohen, C.-H. Lee, K. L. Marshall and I. Daou for their input; B. E. Deverman for advice with AAV vector engineering; K. Deisseroth, D. Gibbs and C. Ramakrishnan for the mScarlet and sfGFP plasmids; J. Stirman and K. Spencer for the imaging support; the staff at Scripps genomics core and Sanford Burnham Prebys histology core for sample preparation; A. Chesler and R. Z. Hill for their feedback on manuscript; and all members of the Ye laboratory, Patapoutian laboratory and Dorris Neuroscience Center for their support and feedback. This work was supported by the Howard Hughes Medical Institute; NIH grants R35 NS105067 and R01AT012051 (to A.P.); NIH Director’s New Innovator Award DP2DK128800 (to L.Y.), NIDDK K01DK114165 (to L.Y.), Whitehall Foundation (to L.Y.) and Baxter Foundation (to L.Y.); Y.W. was supported by the Dorris Scholars fellowship. Y.Z. is a Merck Fellow of the Damon Runyon Cancer Research Foundation, DRG-2405-20. M.D.M.-G. was supported by the Fundacion Alfonso Martin Escudero postdoctoral fellowship.
ASJC Scopus subject areas
- General