Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes
In addition to the endocrine and paracrine systems, peripheral tissues such as gonads, skin, and adipose tissue are involved in the intracrine mechanisms responsible for the formation of sex steroids via the transformation of dehydroepiandrosterone and dehydroepiandrosterone sulfate (DHEA/DHEAS) int...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-04-01
|
| Series: | Frontiers in Molecular Biosciences |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2022.863912/full |
| _version_ | 1828280351829524480 |
|---|---|
| author | Emre Karakus Andreas Schmid Silke Leiting Bärbel Fühler Andreas Schäffler Thilo Jakob Joachim Geyer |
| author_facet | Emre Karakus Andreas Schmid Silke Leiting Bärbel Fühler Andreas Schäffler Thilo Jakob Joachim Geyer |
| author_sort | Emre Karakus |
| collection | DOAJ |
| description | In addition to the endocrine and paracrine systems, peripheral tissues such as gonads, skin, and adipose tissue are involved in the intracrine mechanisms responsible for the formation of sex steroids via the transformation of dehydroepiandrosterone and dehydroepiandrosterone sulfate (DHEA/DHEAS) into potent androgenic and estrogenic hormones. Numerous studies have examined the relationship between overweight, central obesity, and plasma levels of DHEA and DHEAS. The sodium-dependent organic anion transporter Soat (Slc10a6) is a plasma membrane uptake transporter for sulfated steroids. Significantly increased expression of Slc10a6 mRNA has been previously described in organs and tissues of lipopolysaccharide (LPS)-treated mice, including white adipose tissue. These findings suggest that Soat plays a role in the supply of steroids in peripheral target tissues. The present study aimed to investigate the expression of Soat in adipocytes and its role in adipogenesis. Soat expression was analyzed in mouse white intra-abdominal (WAT), subcutaneous (SAT), and brown (BAT) adipose tissue samples and in murine 3T3-L1 adipocytes. In addition, adipose tissue mass and size of the adipocytes were analyzed in wild-type and Slc10a6−/− knockout mice. Soat expression was detected in mouse WAT, SAT, and BAT using immunofluorescence. The expression of Slc10a6 mRNA was significantly higher in 3T3-L1 adipocytes than that of preadipocytes and was significantly upregulated by exposure to lipopolysaccharide (LPS). Slc10a6 mRNA levels were also upregulated in the adipose tissue of LPS-treated mice. In Slc10a6−/− knockout mice, adipocytes increased in size in the WAT and SAT of female mice and in the BAT of male mice, suggesting adipocyte hypertrophy. The serum levels of adiponectin, resistin, and leptin were comparable in wild-type and Slc10a6−/− knockout mice. The treatment of 3T3-L1 adipocytes with DHEA significantly reduced lipid accumulation, while DHEAS did not have a significant effect. However, following LPS-induced Soat upregulation, DHEAS also significantly inhibited lipid accumulation in adipocytes. In conclusion, Soat-mediated import of DHEAS and other sulfated steroids could contribute to the complex pathways of sex steroid intracrinology in adipose tissues. Although in cell cultures the Soat-mediated uptake of DHEAS appears to reduce lipid accumulation, in Slc10a6−/− knockout mice, the Soat deletion induced adipocyte hyperplasia through hitherto unknown mechanisms. |
| first_indexed | 2024-04-13T07:57:00Z |
| format | Article |
| id | doaj.art-9596557c27824cc5a3106399a39a88b5 |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-13T07:57:00Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-9596557c27824cc5a3106399a39a88b52022-12-22T02:55:22ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2022-04-01910.3389/fmolb.2022.863912863912Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 AdipocytesEmre Karakus0Andreas Schmid1Silke Leiting2Bärbel Fühler3Andreas Schäffler4Thilo Jakob5Joachim Geyer6Institute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University, Giessen, GermanyDepartment of Internal Medicine III, Giessen University Hospital, Justus Liebig University, Giessen, GermanyInstitute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University, Giessen, GermanyInstitute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University, Giessen, GermanyDepartment of Internal Medicine III, Giessen University Hospital, Justus Liebig University, Giessen, GermanyDepartment of Dermatology and Allergology, Giessen University Hospital, Justus Liebig University, Giessen, GermanyInstitute of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Justus Liebig University, Giessen, GermanyIn addition to the endocrine and paracrine systems, peripheral tissues such as gonads, skin, and adipose tissue are involved in the intracrine mechanisms responsible for the formation of sex steroids via the transformation of dehydroepiandrosterone and dehydroepiandrosterone sulfate (DHEA/DHEAS) into potent androgenic and estrogenic hormones. Numerous studies have examined the relationship between overweight, central obesity, and plasma levels of DHEA and DHEAS. The sodium-dependent organic anion transporter Soat (Slc10a6) is a plasma membrane uptake transporter for sulfated steroids. Significantly increased expression of Slc10a6 mRNA has been previously described in organs and tissues of lipopolysaccharide (LPS)-treated mice, including white adipose tissue. These findings suggest that Soat plays a role in the supply of steroids in peripheral target tissues. The present study aimed to investigate the expression of Soat in adipocytes and its role in adipogenesis. Soat expression was analyzed in mouse white intra-abdominal (WAT), subcutaneous (SAT), and brown (BAT) adipose tissue samples and in murine 3T3-L1 adipocytes. In addition, adipose tissue mass and size of the adipocytes were analyzed in wild-type and Slc10a6−/− knockout mice. Soat expression was detected in mouse WAT, SAT, and BAT using immunofluorescence. The expression of Slc10a6 mRNA was significantly higher in 3T3-L1 adipocytes than that of preadipocytes and was significantly upregulated by exposure to lipopolysaccharide (LPS). Slc10a6 mRNA levels were also upregulated in the adipose tissue of LPS-treated mice. In Slc10a6−/− knockout mice, adipocytes increased in size in the WAT and SAT of female mice and in the BAT of male mice, suggesting adipocyte hypertrophy. The serum levels of adiponectin, resistin, and leptin were comparable in wild-type and Slc10a6−/− knockout mice. The treatment of 3T3-L1 adipocytes with DHEA significantly reduced lipid accumulation, while DHEAS did not have a significant effect. However, following LPS-induced Soat upregulation, DHEAS also significantly inhibited lipid accumulation in adipocytes. In conclusion, Soat-mediated import of DHEAS and other sulfated steroids could contribute to the complex pathways of sex steroid intracrinology in adipose tissues. Although in cell cultures the Soat-mediated uptake of DHEAS appears to reduce lipid accumulation, in Slc10a6−/− knockout mice, the Soat deletion induced adipocyte hyperplasia through hitherto unknown mechanisms.https://www.frontiersin.org/articles/10.3389/fmolb.2022.863912/fullSOATSlc10a6DHEAStransportknockout mouse3T3-L1 |
| spellingShingle | Emre Karakus Andreas Schmid Silke Leiting Bärbel Fühler Andreas Schäffler Thilo Jakob Joachim Geyer Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes Frontiers in Molecular Biosciences SOAT Slc10a6 DHEAS transport knockout mouse 3T3-L1 |
| title | Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes |
| title_full | Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes |
| title_fullStr | Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes |
| title_full_unstemmed | Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes |
| title_short | Role of the Steroid Sulfate Uptake Transporter Soat (Slc10a6) in Adipose Tissue and 3T3-L1 Adipocytes |
| title_sort | role of the steroid sulfate uptake transporter soat slc10a6 in adipose tissue and 3t3 l1 adipocytes |
| topic | SOAT Slc10a6 DHEAS transport knockout mouse 3T3-L1 |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2022.863912/full |
| work_keys_str_mv | AT emrekarakus roleofthesteroidsulfateuptaketransportersoatslc10a6inadiposetissueand3t3l1adipocytes AT andreasschmid roleofthesteroidsulfateuptaketransportersoatslc10a6inadiposetissueand3t3l1adipocytes AT silkeleiting roleofthesteroidsulfateuptaketransportersoatslc10a6inadiposetissueand3t3l1adipocytes AT barbelfuhler roleofthesteroidsulfateuptaketransportersoatslc10a6inadiposetissueand3t3l1adipocytes AT andreasschaffler roleofthesteroidsulfateuptaketransportersoatslc10a6inadiposetissueand3t3l1adipocytes AT thilojakob roleofthesteroidsulfateuptaketransportersoatslc10a6inadiposetissueand3t3l1adipocytes AT joachimgeyer roleofthesteroidsulfateuptaketransportersoatslc10a6inadiposetissueand3t3l1adipocytes |