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Moreover, many quickly regain fat if they stop treatment. In contrast, time-restricted eating does not restrict calorie intake but instead restricts the time window for eating and prevents obesity in mice and humans. Here we investigated the effects of intermittent\n                  <jats:underline>T<\/jats:underline>\n                  ime-\n                  <jats:underline>R<\/jats:underline>\n                  estricted\n                  <jats:underline>F<\/jats:underline>\n                  eeding (iTRF), which extends lifespan and delays markers of aging, on stored fat in\n                  <jats:italic>Drosophila<\/jats:italic>\n                  . Ten days of iTRF caused significant fat loss relative to\n                  <jats:italic>ad lib<\/jats:italic>\n                  diet, an effect that persisted even after return to\n                  <jats:italic>ad lib<\/jats:italic>\n                  diet. Unlike iTRF-induced lifespan extension, iTRF-induced fat loss did not depend on circadian-regulated autophagy. iTRF treated both diet-induced and genetically induced obesity and significantly reduced lipid droplet size in the fat body (adipose tissue). Instead of causing muscle loss, iTRF increased total and muscle-specific protein levels and enhanced flight performance, suggesting a shift in body composition. We found that iTRF evoked fasting-induced hyperactivity, partially mediated by octopamine, the fly ortholog of the human stress hormone norepinephrine. Ablation of octopaminergic neurons (OANs) prevented iTRF-mediated effects: fat loss, increased protein, and enhanced flight performance. Our results suggest that\n                  <jats:italic>Drosophila<\/jats:italic>\n                  iTRF causes rapid, permanent fat loss and increased muscle function through a \u201cfight or flight\u201d response. Understanding the mechanisms driving differences between\n                  <jats:italic>Drosophila<\/jats:italic>\n                  and human responses to TRE could be critical for identifying effective therapeutic targets for obesity.\n                <\/jats:p>","DOI":"10.64898\/2026.08.05.742897","type":"posted-content","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T02:50:15Z","timestamp":1786416615000},"source":"Crossref","is-referenced-by-count":0,"title":["Time-restricted eating promotes sustained fat loss in\n                  <i>Drosophila<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5568-1059","authenticated-orcid":false,"given":"Jared A.","family":"Gatto","sequence":"first","affiliation":[{"name":"Columbia University Irving Medical Center, Department of Genetics and Development, New York, NY, 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