Metabolites
Glucagon-like Peptide-1 Receptor Agonists Promote Sympathetic Innervation in Mouse Adipose Tissues
By Koukou Fu, Zhangyuzi Deng, Wenjing Wu and 2 others.
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.