PMID- 30681884 OWN - NLM STAT- MEDLINE DCOM- 20200113 LR - 20231213 IS - 1530-6860 (Electronic) IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 33 IP - 4 DP - 2019 Apr TI - Lysine-specific demethylase-2 is distinctively involved in brown and beige adipogenic differentiation. PG - 5300-5311 LID - 10.1096/fj.201801422RR [doi] AB - Transcriptional and epigenetic regulation is fundamentally involved in initiating and maintaining progression of cellular differentiation. The 2 types of thermogenic adipocytes, brown and beige, are thought to be of different origins but share functionally similar phenotypes. Here, we report that lysine-specific demethylase 2 (LSD2) regulates the expression of genes associated with lineage identity during the differentiation of brown and beige adipogenic progenitors in mice. In HB2 mouse brown preadipocytes, short hairpin RNA-mediated knockdown (KD) of LSD2 impaired formation of lipid droplet-containing adipocytes and down-regulated brown adipogenesis-associated genes. Transcriptomic analysis revealed that myogenesis-associated genes were up-regulated in LSD2-KD cells under adipogenic induction. In addition, loss of LSD2 during later phases of differentiation had no obvious influence on adipogenic traits, suggesting that LSD2 functions during earlier phases of brown adipocyte differentiation. Using adipogenic cells from the brown adipose tissues of LSD2-knockout (KO) mice, we found reduced expression of brown adipogenesis genes, whereas myogenesis genes were not affected. In contrast, when LSD2-KO cells from inguinal white adipose tissues were subjected to beige induction, these cells showed a dramatic rise in myogenic gene expression. Collectively, these results suggest that LSD2 regulates distinct sets of genes during brown and beige adipocyte formation.-Takase, R., Hino, S., Nagaoka, K., Anan, K., Kohrogi, K., Araki, H., Hino, Y., Sakamoto, A., Nicholson, T. B., Chen, T., Nakao, M. Lysine-specific demethylase-2 is distinctively involved in brown and beige adipogenic differentiation. FAU - Takase, Ryuta AU - Takase R AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. FAU - Hino, Shinjiro AU - Hino S AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. FAU - Nagaoka, Katsuya AU - Nagaoka K AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. FAU - Anan, Kotaro AU - Anan K AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. FAU - Kohrogi, Kensaku AU - Kohrogi K AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. FAU - Araki, Hirotaka AU - Araki H AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. FAU - Hino, Yuko AU - Hino Y AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. FAU - Sakamoto, Akihisa AU - Sakamoto A AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. FAU - Nicholson, Thomas B AU - Nicholson TB AD - Novartis Institutes for BioMedical Research, Novartis Pharma, Cambridge, Massachusetts, USA. FAU - Chen, Taiping AU - Chen T AD - Department of Epigenetics and Molecular Carcinogenesis, The University of Texas M. D. Anderson Cancer Center, Smithville, Texas, USA. FAU - Nakao, Mitsuyoshi AU - Nakao M AD - Department of Medical Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Japan. LA - eng GR - R01 DK106418/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190125 PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - 0 (PPAR gamma) RN - 0 (RNA, Small Interfering) RN - EC 1.14.11.- (Histone Demethylases) RN - EC 1.14.11.- (KDM1B protein, human) SB - IM MH - Adipogenesis/genetics/physiology MH - Adipose Tissue, Brown/*cytology/*metabolism MH - Animals MH - Blotting, Western MH - Cell Differentiation/genetics/physiology MH - Cells, Cultured MH - Chromatin Immunoprecipitation MH - Female MH - Histone Demethylases/genetics/*metabolism MH - Lentivirus/genetics MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - PPAR gamma/metabolism MH - RNA, Small Interfering/genetics/*metabolism MH - Real-Time Polymerase Chain Reaction PMC - PMC6436657 OTO - NOTNLM OT - LSD2 OT - adipogenesis OT - gene regulation OT - oxidative metabolism COIS- The authors thank Shingo Usuki and Sayoko Fujimura (both of Kumamoto University) for their technical support in RNA-seq and histological analyses, respectively. This work was supported by the following funding sources: Japan Society for the Promotion of Science (JSPS) KAKENHI [JP15H04707 (to M.N.), JP18H02618 (to M.N.), JP16K07215 (to S.H.), and 25430178 (to S.H.)], Takeda Science Foundation (to M.N. and S.H.), The Shinnihon Foundation of Advanced Medical Treatment Research (to S.H.), Ono Medical Research Foundation (to S.H.), Mochida Memorial Foundation for Medical and Pharmaceutical Research (to S.H.), and U.S. National Institutes of Health (NIH) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant 1R01DK106418-01 (to T.C.). The authors declare no conflicts of interest. EDAT- 2019/01/27 06:00 MHDA- 2020/01/14 06:00 PMCR- 2020/04/01 CRDT- 2019/01/26 06:00 PHST- 2019/01/27 06:00 [pubmed] PHST- 2020/01/14 06:00 [medline] PHST- 2019/01/26 06:00 [entrez] PHST- 2020/04/01 00:00 [pmc-release] AID - FJ_201801422RR [pii] AID - 10.1096/fj.201801422RR [doi] PST - ppublish SO - FASEB J. 2019 Apr;33(4):5300-5311. doi: 10.1096/fj.201801422RR. Epub 2019 Jan 25.