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We evaluated the role of melatonin in BAT molecular machinery of male Control, pinealectomized (PINX), and melatonin\u2010treated pinealectomized (PINX\/Mel) adult rats. BAT was collected either every 3\u00a0hours over 24\u00a0hours or after cold or high\u2010fat diet (HFD) acute exposure. HFD PINX animals presented decreased Dio2 expression, while HFD PINX\/Mel animals showed increased Dio2, Ucp1, and Cidea expression. Cold\u2010exposed PINX rats showed decreased Dio2 and Lhs expression, and melatonin treatment augmented Adr\u03b23, Dio2, Ucp1, and Cidea expression. Daily profiles analyses showed altered Dio2, Lhs, Ucp1, Pgc1\u03b1, and Cidea gene and UCP1 protein expression in PINX animals, leading to altered rhythmicity under sub\u2010thermoneutral conditions, which was partially restored by melatonin treatment. The same was observed for mitochondrial complexes I, II, and IV protein expression and enzyme activity. Melatonin absence seems to impair BAT responses to metabolic challenges, and melatonin replacement reverses this effect, with additional increase in the expression of crucial genes, suggesting that melatonin plays an important role in several key points of the thermogenic activation pathway, influencing both the rhythmic profile of the tissue and its ability to respond to metabolic challenges, which is crucial for the organism homeostasis.<\/jats:p>","DOI":"10.1111\/jpi.12549","type":"journal-article","created":{"date-parts":[[2018,12,31]],"date-time":"2018-12-31T23:02:09Z","timestamp":1546297329000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Melatonin multiple effects on brown adipose tissue molecular machinery"],"prefix":"10.1111","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6476-5764","authenticated-orcid":false,"given":"Caroline A. 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