PMID- 32452516 OWN - NLM STAT- MEDLINE DCOM- 20210323 LR - 20210323 IS - 1573-4935 (Electronic) IS - 0144-8463 (Print) IS - 0144-8463 (Linking) VI - 40 IP - 6 DP - 2020 Jun 26 TI - Vitamin D-vitamin D receptor system down-regulates expression of uncoupling proteins in brown adipocyte through interaction with Hairless protein. LID - 10.1042/BSR20194294 [doi] LID - BSR20194294 AB - Our previous study showed that feeding mice with vitamin D deficiency diet markedly alleviated high-fat-diet-induced overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D deficiency up-regulated the expression of uncoupling protein 3 (Ucp3) in white adipose tissue (WAT) and brown adipose tissue (BAT). The present study aimed to further investigate the effects of vitamin D and vitamin D receptor (Vdr) on Ucp1-3 (Ucps) expression in brown adipocyte and the mechanism involved in it. Rat primary brown adipocytes were separated and purified. The effects of the 1,25(OH)2D3 (1,25-dihydroxyvitamin D3; the hormonal form of vitamin D) and Vdr system on Ucps expression in brown adipocytes were investigated in basal condition and activated condition by isoproterenol (ISO) and triiodothyronine (T3). Ucps expression levels were significantly down-regulated by 1,25(OH)2D3 in the activated brown adipocyte. Vdr silencing reversed the down-regulation of Ucps by 1,25(OH)2D3, whereas Vdr overexpression strengthened the down-regulation effects. Hairless protein did express in brown adipocyte and was localized in cell nuclei. 1,25(OH)2D3 increased Hairless protein expression in the cell nuclei. Hairless (Hr) silencing notably elevated Ucps expression in activated condition induced by ISO and T3. Moreover, immunoprecipitation results revealed that Vdr could interact with Hairless, which might contribute to decreasing expression of Vdr target gene Ucps. These data suggest that vitamin D suppresses expression of Ucps in brown adipocyte in a Vdr-dependent manner and the corepressor Hairless protein probably plays a role in the down-regulation. CI - (c) 2020 The Author(s). FAU - Wang, Pei-Qi AU - Wang PQ AD - Department of Pediatrics, First Affiliated Hospital, Anhui Medical University, 218 Jixi Road, Hefei 230 022, Anhui Province, China. FAU - Pan, Dao-Xiang AU - Pan DX AD - Department of Pediatrics, First Affiliated Hospital, Anhui Medical University, 218 Jixi Road, Hefei 230 022, Anhui Province, China. FAU - Hu, Chun-Qiu AU - Hu CQ AD - Department of Toxicology, Anhui Medical University, 81 Meishan Road, Hefei 230 032, Anhui Province, China. FAU - Zhu, Yu-Lin AU - Zhu YL AD - Department of Pediatrics, First Affiliated Hospital, Anhui Medical University, 218 Jixi Road, Hefei 230 022, Anhui Province, China. FAU - Liu, Xiao-Jing AU - Liu XJ AD - Department of Pediatrics, First Affiliated Hospital, Anhui Medical University, 218 Jixi Road, Hefei 230 022, Anhui Province, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Biosci Rep JT - Bioscience reports JID - 8102797 RN - 0 (Mitochondrial Uncoupling Proteins) RN - 0 (Receptors, Calcitriol) RN - 0 (Transcription Factors) RN - 0 (Ucp1 protein, rat) RN - 0 (Ucp2 protein, rat) RN - 0 (Ucp3 protein, rat) RN - 0 (Uncoupling Protein 1) RN - 0 (Uncoupling Protein 2) RN - 0 (Uncoupling Protein 3) RN - 0 (Vitamins) RN - 0 (hr protein, rat) RN - FXC9231JVH (Calcitriol) SB - IM MH - Adipocytes, Brown/*drug effects/metabolism MH - Animals MH - Calcitriol/*pharmacology MH - Cells, Cultured MH - Gene Expression Regulation MH - Male MH - Mitochondrial Uncoupling Proteins/genetics/*metabolism MH - Rats, Sprague-Dawley MH - Rats, Wistar MH - Receptors, Calcitriol/*agonists/genetics/metabolism MH - Signal Transduction MH - Transcription Factors/genetics/*metabolism MH - Uncoupling Protein 1/genetics/metabolism MH - Uncoupling Protein 2/genetics/metabolism MH - Uncoupling Protein 3/genetics/metabolism MH - Vitamins/*pharmacology PMC - PMC7286880 OTO - NOTNLM OT - 1,25(OH)2D3 OT - hairless protein OT - uncoupling proteins OT - vitamin D OT - vitamin D receptor COIS- The authors declare that there are no competing interests associated with the manuscript. EDAT- 2020/05/27 06:00 MHDA- 2021/03/24 06:00 PMCR- 2020/06/10 CRDT- 2020/05/27 06:00 PHST- 2019/12/30 00:00 [received] PHST- 2020/05/13 00:00 [revised] PHST- 2020/05/14 00:00 [accepted] PHST- 2020/05/27 06:00 [pubmed] PHST- 2021/03/24 06:00 [medline] PHST- 2020/05/27 06:00 [entrez] PHST- 2020/06/10 00:00 [pmc-release] AID - 225002 [pii] AID - BSR20194294 [pii] AID - 10.1042/BSR20194294 [doi] PST - ppublish SO - Biosci Rep. 2020 Jun 26;40(6):BSR20194294. doi: 10.1042/BSR20194294.