Downstream interaction by glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide agonism is required for synergistic effects on body weight.

ABSTRACT:

Objectives

Dual glucagon-like peptide-1 receptor and glucose-dependent insulinotropic polypeptide receptor agonists (GLP1RA and GIPRA, respectively) synergise to reduce body weight. Though this synergy depends on receptors within the brain, where and how this occurs is unclear.

Methods

We employed a combination of neuroanatomical approaches in the mouse to investigate access of the dual GLP1RA/GIPRA, tirzepatide, and study the central targets engaged by single agonist, dual agonist and combined agonist treatments. Genetic manipulations were then used to further investigate the functional significance of specific brain regions and distinct neuronal subtypes.

Results

We recorded penetration of fluorescently labelled tirzepatide limited mainly to circumventricular organs

SUBMITTER: Feetham CH 

PROVIDER: S-EPMC12336652 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature