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Though the exact mechanisms underlying GLP-1/GIP synergism are unclear, some hypotheses have suggested that GIP operates directly via the CNS by reducing food intake, increasing the anorexigenic action of GLP-1, or enhancing tolerability to GLP-1R agonists (13)

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This process involves AMPK activation in the hypothalamic ventromedial nucleus by GLP-1 or GLP-1RA, promoting brown adipose tissue thermogenesis and white adipose tissue browning