title: GM13133 is a negative regulator in mouse white adipocytes differentiation and drives the characteristics of brown adipocytes.
abstract: Obesity is tightly associated with the disturbance of white adipose tissue storing excess energy. Thermogenic adipocytes (brown and beige) exert a critical role of oxidizing nutrients at the high rates through non-shivering thermogenesis. The recruitment of brown characteristics in white adipocytes, termed browning, has been considered as a promising strategy for treating obesity and associated metabolic complications. Recently, long noncoding RNAs play a crucial role in regulating tissue development and participating in disease pathogenesis, yet their effects on the conversion of white into brown-like adipocytes and thermogenic function were not totally understood. Here, we identified a mouse brown adipose specific expressed lncRNA, termed GM13133. Moreover, a considerable amount of GM13133 is expressed in adipocytes and actively modulated by cold, β3-adrenergic agonist and cAMP stimuli, implying a potential role in the conversion from white to brown adipocytes. Overexpression of GM13133 did not affect the proliferation of mouse white pre-adipocytes, but inhibited white adipocyte differentiation by decreasing lipid accumulation. The forced expression of GM13133 also significantly drove the conversion of white into brown-like adipocytes with the enhanced mitochondrial biogenesis and the induced expression of brown adipocytes specific markers. A global mRNA analysis further indicated the possible regulatory role of cAMP signaling pathway in GM13133 mediated white-to-brown adipocytes conversion. Our results identified a lncRNA-mediated modulation in primary mouse white adipocyte differentiation and indicate the functional significance of GM13133 in promoting browning of white adipocytes and maintenance of thermogenesis, further providing a potential strategy to treating obesity.
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: LiangHui
authors.initials: L
authors.lastname: You
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: YaHui
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: XianWei
authors.initials: X
authors.lastname: Cui
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: XingYun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, 453003, China.
authors.forename: YaZhou
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Wen
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: Kaipeng
authors.initials: K
authors.lastname: Xie
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.
authors.forename: RanRan
authors.initials: R
authors.lastname: Tang
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: ChenBo
authors.initials: C
authors.lastname: Ji
authors.affiliation: Nanjing Maternity and Child Health Care Institute, Nanjing Maternity and Child Health Care Hospital, Obsterics and Gynecology Hospital Affiliated to Nanjing Medical University, Nanjing, 210004, China.|Institute of Pediatrics, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: XiRong
authors.identifier: http://orcid.org/0000-0002-3873-8233
authors.initials: X
authors.lastname: Guo
mesh_terms: D052437:Adipocytes, Brown / Q000187:drug effects / Q000378:metabolism*; D052438:Adipocytes, White / Q000187:drug effects / Q000378:metabolism*; D050156:Adipogenesis / Q000187:drug effects; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001833:Body Temperature Regulation; D049109:Cell Proliferation; D054338:Cell Transdifferentiation / Q000187:drug effects; D002478:Cells, Cultured; D003080:Cold Temperature; D000242:Cyclic AMP / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D001678:Organelle Biogenesis; D010641:Phenotype; D061251:Primary Cell Culture; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D062085:RNA, Long Noncoding; D022702:Receptors, Adrenergic, beta-3; C000624117:long non coding RNA GM13133, mouse; D000242:Cyclic AMP
keywords: GM13133; browning; differentiation; lncRNA; mitochondria