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Occupancy stays low, but each engaged receptor keeps sending its main message longer than it would under a balanced signal (cAMP bias with low receptor internalization). In a head-to-head trial against liraglutide, tirzepatide reduced measured food intake and craving more despite lower GLP-1 occupancy. The effect lowers the drive to eat rather than increasing restraint

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Discovered in 2015 by Changhan David Lee and Pinchas Cohen at USC, MOTS-c is encoded in the 12S rRNA region of the mitochondrial genomemaking it one of a small but growing family of mitochondrial-derived peptides (MDPs) that challenge the longstanding view of mitochondria as passive energy factories.1 This discovery sheds new light on mitochondria and positions them as active regulators of metabolism. Changhan David Lee, Assistant Professor of Gerontology, USC Leonard Davis School12 The Exercise Connection Human studies show that circulating endogenous MOTS-c levels increase approximately 1.6-fold during exercise and remain elevated about 1.5-fold post-exercise before returning to baseline after roughly four hours.13 This temporal profile suggests MOTS-c functions as an exercise-induced mitokinea signaling molecule released by mitochondria in working muscles that communicates metabolic status to the rest of the body