Overview

• Research highlights distinct mechanisms for GIP receptor agonists and antagonists in reducing weight via separate brain pathways.
• GIPR agonists rely on GABAergic neurons, while antagonists depend on GLP-1R signaling in the hindbrain for their effects.
• A new GIPR-Ab/GLP-1 peptide–antibody conjugate achieves superior weight loss in obese mice through dual brain receptor engagement.
• The conjugate enhances thermogenesis and metabolic rates, suggesting potential for holistic metabolic remodeling.
• Challenges remain for human application, including ensuring brain receptor targeting and managing immunogenicity risks.