The Role of Gas6 Gene in Estrogen Related Adipogenesis
| Autor: | Huang Sheng Kai, 黃聖凱 |
|---|---|
| Rok vydání: | 2015 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 103 Postmenopausal women have an increased tendency for gaining weight. It is known that the physiological withdrawal of estrogen during menopause brings about changes in fat metabolism, together with physical inactivity, are probably the major causes of this phenomenon. However, there is strong evidence that estrogen therapy may partly prevent this menopause-related change in body fat distribution and the associated metabolic sequelae. In addition, previous cell based studies showed estrogen had direct effects on adipocytes to inhibit lipogenesis. Moreover, estrogen also had central effects on food consumption and energy expenditure that contribute to its overall inhibitory effects on adipocyte deposition in animal and human studies. Gas6 is the ligand for the Tyro-3, Axl and Mer (TAM) family of receptors, and Gas6/TAM signaling stimulates cellular responses including activation of AKT,ERK and JAK/STAT pathway. Recent studies indicate that Gas6 is involved in adipocyte development, and human Gas6 gene polymorphisms and plasma Gas6 levels are associated with obesity. Our clinical data showed that significantly lower Gas6 levels in the postmenopausal compared to the premenopausal women, and plasma Gas6 levels were positively correlated with estradiol (E2) levels in the pre- and postmenopausal women. Furthermore, in the previous study revealed that Gas6 gene promoter was found to contain the estrogen response element. Taken together, the regulation mechanism between estrogen 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. At first, we incubated SGBS and 3T3-L1, human and mouse adipocyte cell line, with 17-β estradiol (E2) for 24 hrs. Our data showed increased estrogen receptor α (ERα) and Gas6 expression after E2 treatment in both adipocyte cell lines. Meanwhile, E2 treatment can decrease adipogenesis related genes expression including the fatty acid synthase (FAS), lipoprotein lipase (LPL) and GLUT4 genes in both adipocyte cell lines and influence adipocyte development. Furthermore, we used estrogen antagonism to elucidate the regulation mechanism between estrogen and Gas6 gene in adipocyte. The data revealed that blocked the ERα with estrogen antagonism could reduce Gas6 expression, and then reverse the expression of adipogenesis related genes. In addition, the result of luciferase assay confirmed that Gas6 gene expression was activated after E2 treatment through genomic pathway. However, we found that estrogen may also regulate Gas6 expression through non-genomic AMPK pathway. Finally, in our ovariectomy rat model with or without E2 supplement, the data showed significantly decreased Gas6 expression in adipose tissue from ovariectomy rats compared to the sham operation group. Interesting, the elevated Gas6 expression in adipose tissue was found in ovariectomy rats with E2 supplement. In conclusion, our data first elucidate 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. Meanwhile, our finding might provide a new therapeutic strategy for postmenopausal related obesity by activating Gas6 expression in adipose tissue especially in women which can’t receive long term estrogen treatment. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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