Loss of GIP receptor in leptin receptor cells reduces glucose control by GIP and GIP-GLP-1 combination without changing body weight or food intake in mice

GIPR signaling in leptin receptor-expressing cells does not affect body weight or food intake in diet-induced obesity mice.

• GIPR and leptin receptors show strong co-expression in the pancreas, but not in the hypothalamus or hindbrain.
• Mice lacking Gipr in leptin receptor-expressing cells exhibit similar body weight and food intake as wildtype mice under diet-induced obesity conditions.
• Both acyl-GIP and the GIPR:GLP-1R co-agonist MAR709 effectively reduce body weight and food intake in the absence of GIPR signaling in leptin receptor cells.
• The enhanced glycemic effect of GIPR:GLP-1R co-agonism compared to single GLP-1R agonism is lost in leptin receptor-GIPR knockout mice.

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