Progesterone receptor membrane associated component 1 enhances obesity progression in mice by facilitating lipid accumulation in adipocytes

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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Reporting for specific materials, systems and methods  anti-PPAR gamma antibody (Abcam: ab59256) was validated for detection of mouse PPAR gamma by WB. anti-FABP4 antibody (Abcam: ab66682) was validated for detection of mouse FABP4 by WB. anti-LDL-R antibody for western blotting (R&D: AF2255) was validated for detection of mouse LDL-R by WB. anti-VLDL-R antibody (R&D: AF2258) was validated for detection of mouse VLDL-R by WB. anti-Tf-R antibody (Abcam: ab84039) was validated for detection of mouse Tf-R by WB. anti-Na-K ATPase alpha1 antibody (Abcam: ab7671) was validated for detection of mouse Na-K ATPase alpha1 by WB. anti-GLUT1 antibody (Abcam: ab115730) was validated for detection of mouse GLUT1 by WB. anti-GLUT4 antibody (Abcam: ab33780) was validated for detection of mouse GLUT4 by WB. anti-Akt antibody (Cell signaling: #9272S) was validated for detection of mouse Akt by WB. anti-pAkt antibody (Cell signaling: #4060S) was validated for detection of mouse pAkt by WB. anti-HO-1 antibody(Santa Cruz Biotechnology: sc-136960) was validated for detection of mouse HO-1 by WB. Note that full information on the approval of the study protocol must also be provided in the manuscript.

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