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LepR-Lineage Cells Represent the Main Target of the Nociceptive CGRP Pathway in White Adipose Tissue Browning.

Overview

Authors: Yu‐Ting Yen1, May Chien1, Yan‐Tung Kiu1, Ru‐Sing Lee1, Hui‐Teng Cheng2, Shuei‐Liong Lin3, Dong‐Chuan Wu4,5, I‐Hsien Teng4,5, Yi‐Wen Lin6, Yi‐Hung Chen6, Mien‐Chie Hung4,7, Shih‐Chieh Hung1,8,9,10
ORCID iDs: Yu‐Ting Yen, Ru‐Sing Lee, Hui‐Teng Cheng, Shuei‐Liong Lin, Yi‐Wen Lin, Yi‐Hung Chen, Mien‐Chie Hung, Shih‐Chieh Hung
  1. Drug Development Center, Institute of Translational Medicine and New Drug Development, School of Medicine, China Medical University, Taichung, Taiwan
  2. Department of Internal Medicine, National Taiwan University Hospital Hsin‐Chu Branch, Zhubei City, Taiwan
  3. Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan
  4. Graduate Institute of Biomedical Sciences, Research Center for Cancer Biology, China Medical University, Taichung, Taiwan
  5. Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan
  6. Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan
  7. Center For Molecular Medicine, China Medical University Hospital, Taichung, Taiwan
  8. College of Life Sciences, China Medical University, Taichung, Taiwan
  9. Integrative Stem Cell Center, China Medical University Hospital, Taichung, Taiwan
  10. Department of Orthopaedics, China Medical University Hospital, Taichung, Taiwan
Institutions: China Medical University (Taiwan); China Medical University (China); National Taiwan University Hospital (Taiwan); National Taiwan University (Taiwan); China Medical University Hospital (Taiwan)
Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany), article e78714
Dates: received 4 June 2026; accepted 30 October 2026; published online 9 November 2026; in print November 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1002/advs.78714 · PMID 43004754 · PMCID PMC13748883 · OpenAlex W4408364628
Open access: gold, a free copy (OpenAlex)
Preprint: doi:10.21203/rs.3.rs-5971709/v1
Status: data only (how the code is found and verified)
Categories: pain (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Evoked potentials, fMRI & imaging
Keywords: adipose progenitors, CGRP signaling, LepR‐lineage cells, nociceptive innervation, thermogenesis, TRP channels, white adipose tissue browning
Topic: Adipose Tissue and Metabolism (Physiology (medical), Medicine), according to OpenAlex
Funding: China Medical University, Taiwan (CMU111-N-29, CMU110-Z-05); National Science and Technology Council (NSTC112-2320-B-039-007-MY2, NSTC113-2314-B-039-065); China Medical University Hospital (DMR-111-233); Ministry of Science and Technology, Taiwan (MOST109-2314-B-039-009-MY3, MOST111-2326-B-039-001)
Citations: not cited yet (Europe PMC); 78 references in the paper

Abstract

Sympathetic innervation regulates white adipose tissue (WAT) browning; however, the roles of nociceptive neurons and their associated target cells remain unknown. Here, we used single‐nucleus RNA sequencing to profile adipose populations and genetic lineage tracing to identify LepR‐lineage stromal/progenitor cells contributing to cold‐induced WAT browning. Ablation of these cells using LepR‐Cre‐inducible DTR transgenic mice resulted in a decrease in the percentage of UCP1+ cells under cold conditions. The WAT browning process is controlled by peripheral nociceptive nerve‐derived calcitonin gene‐related peptide (CGRP), which was associated with reduced WAT browning and loss of LepR‐lineage cells during intermittent fasting (IF), but not during cold exposure. Local antagonist experiments targeting the transient receptor potential cation channels TRPV1 and TRPM8 were associated with opposing changes in CGRP immunoreactivity and WAT browning. These findings support a condition‐dependent role for nociceptive CGRP signaling in WAT remodeling.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

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Data

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Data Availability Statement

The data that support the findings of this study are openly available in NCBI Gene Expression Omnibus (GEO) at https://www.ncbi.nlm.nih.gov/geo/, reference number GSE217290 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE217290); GSE216925 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE216925).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 12 November 2026: the first record

Recorded: type, language, journal, pages, dates, 12 authors, 7 keywords, 4 funders, 78 references.

Cite

This paper

Yen, Y., Chien, M., Kiu, Y., Lee, R., Cheng, H., Lin, S., Wu, D., Teng, I., Lin, Y., Chen, Y., Hung, M., & Hung, S. (2026). LepR-Lineage Cells Represent the Main Target of the Nociceptive CGRP Pathway in White Adipose Tissue Browning. Advanced science (Weinheim, Baden-Wurttemberg, Germany), e78714. https://doi.org/10.1002/advs.78714

BibTeX

@article{yen2026lepr,
author = {Yen, Yu‐Ting and Chien, May and Kiu, Yan‐Tung and Lee, Ru‐Sing and Cheng, Hui‐Teng and Lin, Shuei‐Liong and Wu, Dong‐Chuan and Teng, I‐Hsien and Lin, Yi‐Wen and Chen, Yi‐Hung and Hung, Mien‐Chie and Hung, Shih‐Chieh},
title = {{LepR-Lineage Cells Represent the Main Target of the Nociceptive CGRP Pathway in White Adipose Tissue Browning}},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = nov,
pages = {e78714},
publisher = {Wiley},
issn = {2198-3844},
doi = {10.1002/advs.78714},
url = {https://doi.org/10.1002/advs.78714},
pmid = {43004754},
pmcid = {PMC13748883}
}

RIS

TY - JOUR
AU - Yen, Yu‐Ting
AU - Chien, May
AU - Kiu, Yan‐Tung
AU - Lee, Ru‐Sing
AU - Cheng, Hui‐Teng
AU - Lin, Shuei‐Liong
AU - Wu, Dong‐Chuan
AU - Teng, I‐Hsien
AU - Lin, Yi‐Wen
AU - Chen, Yi‐Hung
AU - Hung, Mien‐Chie
AU - Hung, Shih‐Chieh
TI - LepR-Lineage Cells Represent the Main Target of the Nociceptive CGRP Pathway in White Adipose Tissue Browning
T2 - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
J2 - Adv Sci (Weinh)
PY - 2026
DA - 2026/11/09
SP - e78714
SN - 2198-3844
PB - Wiley
DO - 10.1002/advs.78714
UR - https://doi.org/10.1002/advs.78714
LA - en
ER -

CSL-JSON

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