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Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms of circadian rhythm\u2010mediated proliferation in adipose tissue is still limited. Here, we showed that melatonin (20\u00a0mg\/kg\/d) promoted circadian and proliferation processes in white adipose tissue. The circadian amplitudes of <jats:italic>brain and muscle aryl hydrocarbon receptor nuclear translocator\u2010like 1<\/jats:italic> (<jats:italic>Bmal1<\/jats:italic>,<jats:italic> P<\/jats:italic>&lt;.05) and <jats:italic>circadian locomotor output cycles kaput<\/jats:italic> (<jats:italic>Clock<\/jats:italic>,<jats:italic> P<\/jats:italic>&lt;.05), <jats:italic>period 2<\/jats:italic> (<jats:italic>Per2<\/jats:italic>,<jats:italic> P<\/jats:italic>&lt;.05), <jats:italic>cyclin E<\/jats:italic> (<jats:italic>P<\/jats:italic>&lt;.05), and <jats:italic>c\u2010Myc<\/jats:italic> (<jats:italic>P<\/jats:italic>&lt;.05) were directly increased by melatonin in adipose tissue. Melatonin also promoted cell cycle and increased cell numbers (<jats:italic>P<\/jats:italic>&lt;.05), which was correlated with the <jats:italic>Clock<\/jats:italic> expression (<jats:italic>P<\/jats:italic>&lt;.05). Further analysis demonstrated that Clock bound to the E\u2010box elements in the promoter region of <jats:italic>c\u2010Myc<\/jats:italic> and then directly stimulated <jats:italic>c\u2010Myc<\/jats:italic> transcription. Moreover, Clock physically interacted with histone deacetylase 3 (<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>3) and formed a complex with c\u2010Myc to promote adipocyte proliferation. Melatonin also attenuated circadian disruption and promoted adipocyte proliferation in chronic jet\u2010lagged mice and obese mice. Thus, our study found that melatonin promoted adipocyte proliferation by forming a Clock\/<jats:styled-content style=\"fixed-case\">HDAC<\/jats:styled-content>3\/c\u2010Myc complex and subsequently driving the circadian amplitudes of proliferation genes. Our data reveal a novel mechanism that links circadian rhythm to cell proliferation in adipose tissue. These findings also identify a new potential means for melatonin to prevent and treat sleep deprivation\u2010caused obesity.<\/jats:p>","DOI":"10.1111\/jpi.12383","type":"journal-article","created":{"date-parts":[[2016,12,17]],"date-time":"2016-12-17T22:27:03Z","timestamp":1482013623000},"source":"Crossref","is-referenced-by-count":77,"title":["Melatonin promotes circadian rhythm\u2010induced proliferation through <scp>C<\/scp>lock\/histone deacetylase 3\/c\u2010<scp>M<\/scp>yc interaction in mouse adipose tissue"],"prefix":"10.1111","volume":"62","author":[{"given":"Zhenjiang","family":"Liu","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Gan","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Luo","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7222-4028","authenticated-orcid":false,"given":"Chao","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Animal Science and Technology Northwest A&amp;F University  Yangling Shaanxi China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,3,21]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"793","article-title":"Chronic sleep deprivation and seasonality: implications for the obesity epidemic","volume":"34","author":"Cizza G","year":"2011","journal-title":"J Endocrinol 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