TY - JOUR
T1 - Progesterone receptor membrane associated component 1 enhances obesity progression in mice by facilitating lipid accumulation in adipocytes
AU - Furuhata, Ryogo
AU - Kabe, Yasuaki
AU - Kanai, Ayaka
AU - Sugiura, Yuki
AU - Tsugawa, Hitoshi
AU - Sugiyama, Eiji
AU - Hirai, Miwa
AU - Yamamoto, Takehiro
AU - Koike, Ikko
AU - Yoshikawa, Noritada
AU - Tanaka, Hirotoshi
AU - Koseki, Masahiro
AU - Nakae, Jun
AU - Matsumoto, Morio
AU - Nakamura, Masaya
AU - Suematsu, Makoto
N1 - Funding Information:
This research was supported by AMED-CREST (to Y.K., Grant No.: JP17gm0710010), JSPS KAKENHI (to Y.K., Grant No.: 18K06921). This study was supported partly by JST ERATO Suematsu Gas Biology Project (until March 2015).
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Progesterone receptor membrane associated component 1 (PGRMC1) exhibits haem-dependent dimerization on cell membrane and binds to EGF receptor and cytochromes P450 to regulate cancer proliferation and chemoresistance. However, its physiological functions remain unknown. Herein, we demonstrate that PGRMC1 is required for adipogenesis, and its expression is significantly enhanced by insulin or thiazolidine, an agonist for PPARγ. The haem-dimerized PGRMC1 interacts with low-density lipoprotein receptors (VLDL-R and LDL-R) or GLUT4 to regulate their translocation to the plasma membrane, facilitating lipid uptake and accumulation, and de-novo fatty acid synthesis in adipocytes. These events are cancelled by CO through interfering with PGRMC1 dimerization. PGRMC1 expression in mouse adipose tissues is enhanced during obesity induced by a high fat diet. Furthermore, adipose tissue-specific PGRMC1 knockout in mice dramatically suppressed high-fat-diet induced adipocyte hypertrophy. Our results indicate a pivotal role of PGRMC1 in developing obesity through its metabolic regulation of lipids and carbohydrates in adipocytes.
AB - Progesterone receptor membrane associated component 1 (PGRMC1) exhibits haem-dependent dimerization on cell membrane and binds to EGF receptor and cytochromes P450 to regulate cancer proliferation and chemoresistance. However, its physiological functions remain unknown. Herein, we demonstrate that PGRMC1 is required for adipogenesis, and its expression is significantly enhanced by insulin or thiazolidine, an agonist for PPARγ. The haem-dimerized PGRMC1 interacts with low-density lipoprotein receptors (VLDL-R and LDL-R) or GLUT4 to regulate their translocation to the plasma membrane, facilitating lipid uptake and accumulation, and de-novo fatty acid synthesis in adipocytes. These events are cancelled by CO through interfering with PGRMC1 dimerization. PGRMC1 expression in mouse adipose tissues is enhanced during obesity induced by a high fat diet. Furthermore, adipose tissue-specific PGRMC1 knockout in mice dramatically suppressed high-fat-diet induced adipocyte hypertrophy. Our results indicate a pivotal role of PGRMC1 in developing obesity through its metabolic regulation of lipids and carbohydrates in adipocytes.
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U2 - 10.1038/s42003-020-01202-x
DO - 10.1038/s42003-020-01202-x
M3 - Article
C2 - 32887925
AN - SCOPUS:85090268924
VL - 3
JO - Communications Biology
JF - Communications Biology
SN - 2399-3642
IS - 1
M1 - 479
ER -