Background: The physiological withdrawal of estrogen during menopause brings about changes in fat metabolism. Previous cell-based studies showed estrogen had direct effects on adipocytes. Gas6 is the ligand for the Tyro-3, Axl and Mer (TAM) receptors, and Gas6/TAM signaling stimulates cellular responses. Recent studies indicate that Gas6 gene was involved in adipocyte development, and human Gas6 levels were associated with obesity. Our clinical data showed Gas6 levels were positively correlated with estradiol (E2) levels in the postmenopausal women. However, the regulation mechanism between E2 and Gas6 gene in adipocyte functions is still unknown. In this study, we try to investigate the possible role of Gas6 gene that involved in estrogen effect on adipocyte development.

Materials and Methods: Human and mouse adipocyte cell lines, SGBS and 3T3-L1, were used as in vitro cell model and ovariectomy rat was used as the postmenopausal animal model.

Results: Our data showed increased estrogen receptor α (ERα) and Gas6 expression after E2 treatment in both SGBS and 3T3-L1 cell lines. Meanwhile, E2 treatment can decrease adipogenesis-related genes expression. Furthermore, we used estrogen antagonism in adipocyte that blocked the ERα and then reduced Gas6 expression and reversed the expression of adipogenesis-related genes. The luciferase assay confirmed that Gas6 gene expression was activated after E2 treatment through the genomic pathway. In addition, estrogen may also regulate Gas6 expression through non-genomic AMPK pathway. Finally, our animal model data showed significantly decreased Gas6 expression in adipose tissue from ovariectomy rats compared to the sham operation group. Interesting, the Gas6 expression in adipose tissue was increased in ovariectomy rats after E2 supplement.

Conclusion: Our study first elucidates the E2 effect on adipogenesis-related genes expression and adipocyte function and may partially through genomic and non-genomic pathways to activate Gas6 gene expression.


C. Lee: None.

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