Membrane and nuclear estrogen receptor α collaborate to suppress adipogenesis but not triglyceride content

Area of Science:

• Endocrinology
• Molecular Biology
• Metabolic Research

Background:

• Estrogen and estrogen receptor alpha (ER-α) are known to inhibit visceral fat accumulation.
• The precise mechanisms by which ER-α exerts these effects across different cellular compartments remain unclear.

Purpose of the Study:

• To elucidate the distinct roles of nuclear and extranuclear ER-α in suppressing visceral fat development.
• To identify the signaling pathways involved in ER-α-mediated inhibition of adipogenesis and lipid synthesis.

Main Methods:

• Utilized genetically modified mice expressing only nuclear ER-α (NOER) or membrane ER-α (MOER).
• Assessed visceral fat deposition and body weight in NOER, MOER, and wild-type (WT) mice.
• Investigated the effects of 17-β-estradiol (E2) on bone marrow stem cell (BMSC) differentiation and adipogenesis in vitro.
• Analyzed gene expression related to adipocyte differentiation and lipid synthesis.

Main Results:

• Mice lacking either nuclear or membrane ER-α exhibited significant abdominal visceral fat deposition and weight gain compared to WT mice.
• E2 suppressed BMSC differentiation into adipocytes in WT mice, but this effect was abolished in NOER and MOER mice.
• Membrane ER-α signaling inhibited triglyceride content in differentiated adipocytes by suppressing carbohydrate response element-binding protein-α and -β via kinase pathways.

Conclusions:

• Both nuclear and extranuclear ER-α play collaborative roles in suppressing adipocyte development.
• Extranuclear ER-α signaling is primarily responsible for inhibiting lipid synthesis in mature adipocytes.
• Nuclear ER-α is not involved in the inhibition of lipid synthesis in mature adipocytes.