Progesterone Receptor Membrane Associated Component 1 Enhances Obesity Progression in Mice by Facilitating Lipid Accumulation in Adipocytes

Overview

Journal Commun Biol

Specialty Biology

Date 2020 Sep 5

PMID 32887925

Citations 16

Authors

Ryogo Furuhata

Yasuaki Kabe

Ayaka Kanai

Yuki Sugiura

Hitoshi Tsugawa

Eiji Sugiyama

Miwa Hirai

Takehiro Yamamoto

Ikko Koike

Noritada Yoshikawa

Hirotoshi Tanaka

Masahiro Koseki

Jun Nakae

Morio Matsumoto

Masaya Nakamura

Makoto Suematsu

Affiliations

Soon will be listed here.

Abstract

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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