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Systemic GLP-1 receptor deficiency impairs GLP-1-induced anorexia as anticipated.41 However, these mice do not display alterations in baseline body weight, suggesting that GLP-1 receptor is not critical for body weight regulation under basal conditions.41 Notably, subsequent investigations revealed that both male and female mice lacking systemic GLP-1 receptor are resistant to diet-induced obesity.39,42 Focusing on central mechanisms, intracerebroventricular administration of GLP-1 failed to modulate feeding behavior in GLP-1 receptor global knockout mice.41 Central inhibition of GLP-1 receptor disrupts glucose homeostasis and reduces food intake, whereas peripheral GLP-1 receptor inactivation impairs glucose-stimulated insulin secretion, diminishes glucose clearance, elevates glucagon levels, and accelerates gastric emptying