ID: 10000. Title: Postdoctoral Research Associate. Application Deadline:

Tirzepatide, a dual agonist of the glucagon-like peptide 1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR), represents a new class of medication for obesity and type II diabetes treatment. Using laboratory mice, we show that GIPRs are present in the lateral septum (LS) in cells also expressing GLP-1R, particularly in the dorsolateral LS. Likewise, we show the coexpression of the dopamine (DA) D2 receptor (DRD2) in LS cells with GLP-1R in both the dorsolateral and intermediate portions of the LS. Using fast-scan cyclic voltammetry, we demonstrate that systemic GLP-1R or GIPR agonist treatment reduces both electrically evoked DA release in the LS and the ability of cocaine to increase extracellular DA levels. These data unveil a new central role for GIPR signaling and identify a potentially important cell type expressing both GLP-1R and GIPR upon which tirzepatide or other dual agonists may modulate DA homeostasis in the brain.

Here the authors show that endogenous or therapeutically delivered GDF-15 activates brainstem neurons that trigger splenic β-adrenergic signaling. This, in turn, suppresses autoreactive T cells and re...