Specific loss of GIPR signaling in GABAergic neurons enhances GLP-1R agonist-induced body weight loss.

ABSTRACT:

Objectives

Dual incretin agonists are among the most effective pharmaceutical treatments for obesity and type 2 diabetes to date. Such therapeutics can target two receptors, such as the glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor in the case of tirzepatide, to improve glycemia and reduce body weight. Regarding body weight effects, GIPR signaling is thought to involve at least two relevant mechanisms: the enhancement of food intake reduction and the attenuation of aversive effects caused by GLP-1R agonists. Although it is known that dual GLP-1R-GIPR agonism produces greater weight loss than GLP-1R agonism alone, the precise mechanism is unknown.

Methods

To address this question, we used mice lacking GIPR in the

SUBMITTER: Wean J 

PROVIDER: S-EPMC11946504 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature