TY - JOUR
T1 - Lysine-specific demethylase-2 is distinctively involved in brown and beige adipogenic differentiation
AU - Takase, Ryuta
AU - Hino, Shinjiro
AU - Nagaoka, Katsuya
AU - Anan, Kotaro
AU - Kohrogi, Kensaku
AU - Araki, Hirotaka
AU - Hino, Yuko
AU - Sakamoto, Akihisa
AU - Nicholson, Thomas B.
AU - Chen, Taiping
AU - Nakao, Mitsuyoshi
N1 - Publisher Copyright:
© FASEB
PY - 2019
Y1 - 2019
N2 - 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. Tran-scriptomic 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.
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. Tran-scriptomic 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.
KW - Adipogenesis gene regulation
KW - LSD2
KW - Oxidative metabolism
UR - http://www.scopus.com/inward/record.url?scp=85064124920&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064124920&partnerID=8YFLogxK
U2 - 10.1096/fj.201801422RR
DO - 10.1096/fj.201801422RR
M3 - Article
C2 - 30681884
AN - SCOPUS:85064124920
SN - 0892-6638
VL - 33
SP - 5300
EP - 5311
JO - FASEB Journal
JF - FASEB Journal
IS - 4
ER -