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Admittedly, melatonin\u2010mediated positive effects on various tissues\/organs have been respectively reported, but regulatory mechanisms of melatonin on the crosstalk between adipose tissue and liver have been investigated rarely. Overall, we hypothesize that the crosstalk originating from adipose tissue may be another worthy regulatory pathway for melatonin ameliorating of hepatic steatosis. Here, we first found the amount of adipocyte\u2010derived exosomal resistin to be significantly decreased by melatonin supplementation. Compared to mice with Exos\n                    <jats:sub>HFD<\/jats:sub>\n                    or Exos\n                    <jats:sub>resistin<\/jats:sub>\n                    treatment, Exos\n                    <jats:sub>MT<\/jats:sub>\n                    remarkably ameliorated hepatic steatosis. Further test demonstrated that resistin was a pivotal cytokine which repressed phosphorylation of 5\u2032 adenosine monophosphate\u2010activated protein kinase \u03b1 (\n                    <jats:styled-content style=\"fixed-case\">pAMPK<\/jats:styled-content>\n                    \u03b1 Thr\n                    <jats:sup>172<\/jats:sup>\n                    ) to trigger endoplasmic reticulum (\n                    <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                    ) stress, resulting in hepatic steatosis, whereas Exos\n                    <jats:sub>MT<\/jats:sub>\n                    reversed these risks in hepatocytes. In adipocytes, we identified melatonin to reduce the production of resistin through the brain and muscle arnt\u2010like protein 1 (Bmal1) transcriptional inhibition. Notably, we also confirmed that melatonin enhanced N\n                    <jats:sup>6<\/jats:sup>\n                    \u2010Methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A)\n                    <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                    demethylation to degrade resistin\n                    <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                    in adipocytes. Overall, melatonin decreases traffic volume of adipocyte\u2010generated exosomal resistin from adipocytes to hepatocytes, which further alleviates\n                    <jats:styled-content style=\"fixed-case\">ER<\/jats:styled-content>\n                    stress\u2010induced hepatic steatosis. Our findings illustrate a novel melatonin\u2010mediated regulatory pathway from adipocytes to hepatocytes, indicating that adipocyte\u2010derived exosome is a new potential target for treating obesity and related hepatorenal syndrome.\n                  <\/jats:p>","DOI":"10.1111\/jpi.12561","type":"journal-article","created":{"date-parts":[[2019,1,19]],"date-time":"2019-01-19T15:06:50Z","timestamp":1547910410000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Reduced delivery of epididymal adipocyte\u2010derived exosomal resistin is essential for melatonin ameliorating hepatic steatosis in mice"],"prefix":"10.1111","volume":"66","author":[{"given":"Bohan","family":"Rong","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Northwest A&amp;F University Yangling Shaanxi 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