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Prior studies have demonstrated increased appetite as well as metabolic adaptations, such as increased energy efficiency, in response to weight loss. However, previous study designs utilized experimentally determined weight loss plateaus and did not investigate spontaneously occurring plateaus nor study participants in their natural, free-living, environments during weight loss. The\n                    <jats:italic>Assessing Diet, Appetite, and Physiology Throughout weight loss<\/jats:italic>\n                    (ADAPT) study was designed to address these limitations of prior research and elucidate mechanistic factors involved in spontaneous cessation of intentional weight loss in humans. ADAPT enrolls participants with obesity who undergo behavioral weight loss via a reduced calorie diet and increased physical activity. Participants\u2019 daily weight is monitored remotely, and new analytic approaches identify weight-loss phases in real time so that study assessments can be targeted to each participants\u2019 individualized trajectory during dynamic weight loss. Deep phenotyping of participants includes anthropometric, metabolic, neurophysiologic, and behavioral assessments; physical activity and physiologic monitoring via wearable devices; and serial sampling of biological tissues such as blood, adipose tissue, and muscle. In summary, the ADAPT study design is generating a uniquely informative and integrative dataset for deepening understanding of the biological mechanisms that halt behaviorally-induced weight loss and thereby limit its long-term health benefits for patients with obesity. 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