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Peer-reviewedCC BY 4.0Metabolites

Glucagon-like Peptide-1 Receptor Agonists Promote Sympathetic Innervation in Mouse Adipose Tissues

  • Koukou Fu1
  • Zhangyuzi Deng1
  • Wenjing Wu1
  • Jing Yang1,2
  • Ying Cao1
  1. 1School of Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University Third Hospital, Peking University, Beijing 100871, China
  2. 2Peking Union Medical College Hospital, Beijing 100730, China
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Abstract

Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used to treat obesity. However, their mechanism of action on adipose tissues remains incompletely understood. Methods: We exploited advanced three-dimensional imaging to investigate the effects of GLP-1RAs on sympathetic innervation in mouse adipose tissues. Results: Semaglutide or tirzepatide robustly promotes sympathetic innervation in inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) but not in the liver tissues of mice with high-fat diet (HFD)-induced obesity. In addition, the sympathetic-promoting effect of tirzepatide occurs in the iWAT and iBAT of aged mice. Conversely, pharmacological ablation of sympathetic inputs results in alterations in adipocyte morphology and metabolic markers in GLP-1RA-treated HFD-fed mice. Moreover, GLP-1R is detected in neurons in the paraventricular nucleus of the hypothalamus of mice, a key brain region that elicits peripheral sympathetic signals, and semaglutide can effectively activate those neurons. Conclusions: These results provide new insights into the potential involvement of sympathetic action in adipose response to GLP-1RA treatment.

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Cite

BibTeXRIS
BibTeX
@article{fu2026glucagonlike,
  title = {{Glucagon-like Peptide-1 Receptor Agonists Promote Sympathetic Innervation in Mouse Adipose Tissues}},
  author = {Koukou Fu and Zhangyuzi Deng and Wenjing Wu and Jing Yang and Ying Cao},
  journal = {Metabolites},
  year = {2026},
  month = oct,
  doi = {10.3390/metabo16110813},
  url = {https://www.mdpi.com/2218-1989/16/11/813},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Glucagon-like Peptide-1 Receptor Agonists Promote Sympathetic Innervation in Mouse Adipose Tissues
AU  - Koukou Fu
AU  - Zhangyuzi Deng
AU  - Wenjing Wu
AU  - Jing Yang
AU  - Ying Cao
PY  - 2026
DA  - 2026/10/26
JO  - Metabolites
DO  - 10.3390/metabo16110813
UR  - https://www.mdpi.com/2218-1989/16/11/813
AB  - Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used to treat obesity. However, their mechanism of action on adipose tissues remains incompletely understood. Methods: We exploited advanced three-dimensional imaging to investigate the effects of GLP-1RAs on sympathetic innervation in mouse adipose tissues. Results: Semaglutide or tirzepatide robustly promotes sympathetic innervation in inguinal white adipose tissue (iWAT) and interscapular brown adipose tissue (iBAT) but not in the liver tissues of mice with high-fat diet (HFD)-induced obesity. In addition, the sympathetic-promoting effect of tirzepatide occurs in the iWAT and iBAT of aged mice. Conversely, pharmacological ablation of sympathetic inputs results in alterations in adipocyte morphology and metabolic markers in GLP-1RA-treated HFD-fed mice. Moreover, GLP-1R is detected in neurons in the paraventricular nucleus of the hypothalamus of mice, a key brain region that elicits peripheral sympathetic signals, and semaglutide can effectively activate those neurons. Conclusions: These results provide new insights into the potential involvement of sympathetic action in adipose response to GLP-1RA treatment.
SN  - 2218-1989
ER  -