Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages
Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for metabolic syndrome including diabetes, obesity, and cardiovascular events. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2018/3062319 |
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| author | Hiroki Yamazaki Akifumi Kushiyama Hideyuki Sakoda Midori Fujishiro Takeshi Yamamotoya Yusuke Nakatsu Takako Kikuchi Sunao Kaneko Hirotoshi Tanaka Tomoichiro Asano |
| author_facet | Hiroki Yamazaki Akifumi Kushiyama Hideyuki Sakoda Midori Fujishiro Takeshi Yamamotoya Yusuke Nakatsu Takako Kikuchi Sunao Kaneko Hirotoshi Tanaka Tomoichiro Asano |
| author_sort | Hiroki Yamazaki |
| collection | DOAJ |
| description | Sex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for metabolic syndrome including diabetes, obesity, and cardiovascular events. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains unknown. In this study, using adipocytes and macrophages, we focused on the in vitro effects of SHBG on inflammation as well as lipid metabolism. Incubation with 20 nM SHBG markedly suppressed lipopolysaccharide- (LPS-) induced inflammatory cytokines, such as MCP-1, TNFα, and IL-6 in adipocytes and macrophages, along with phosphorylations of JNK and ERK. Anti-inflammatory effects were also observed in 3T3-L1 adipocytes cocultured with LPS-stimulated macrophages. In addition, SHBG treatment for 18 hrs or longer significantly induced the lipid degradation of differentiated 3T3-L1 cells, with alterations in its corresponding gene and protein levels. Notably, these effects of SHBG were not altered by coaddition of large amounts of testosterone or estradiol. In conclusion, SHBG suppresses inflammation and lipid accumulation in macrophages and adipocytes, which might be among the mechanisms underlying the protective effect of SHBG, that is, its actions which reduce the incidence of metabolic syndrome. |
| format | Article |
| id | doaj-art-5ad4de17bb5e43d0bb57a4f086cd32e2 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-5ad4de17bb5e43d0bb57a4f086cd32e22025-02-03T01:11:28ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/30623193062319Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and MacrophagesHiroki Yamazaki0Akifumi Kushiyama1Hideyuki Sakoda2Midori Fujishiro3Takeshi Yamamotoya4Yusuke Nakatsu5Takako Kikuchi6Sunao Kaneko7Hirotoshi Tanaka8Tomoichiro Asano9Department of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, JapanDivision of Diabetes and Metabolism, Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Bakuro-cho, Chuo-ku, Tokyo 103-0002, JapanDivision of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake-cho, Miyazaki, Miyazaki 889-1692, JapanDivision of Diabetes and Metabolic Diseases, Nihon University School of Medicine, 30-1, Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, JapanDepartment of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 734-8551, JapanDepartment of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 734-8551, JapanDivision of Diabetes and Metabolism, Institute for Adult Diseases, Asahi Life Foundation, 2-2-6, Bakuro-cho, Chuo-ku, Tokyo 103-0002, JapanDepartment of Diabetes and Metabolic Diseases, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, JapanDepartment of Rheumatology and Allergy, IMSUT Hospital, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, JapanDepartment of Medical Science, Graduate School of Medicine, University of Hiroshima, 1-2-3 Kasumi, Minami-ku, Hiroshima, Hiroshima 734-8551, JapanSex hormone-binding globulin (SHBG) is a serum protein released mainly by the liver, and a low serum level correlates with a risk for metabolic syndrome including diabetes, obesity, and cardiovascular events. However, the underlying molecular mechanism(s) linking SHBG and metabolic syndrome remains unknown. In this study, using adipocytes and macrophages, we focused on the in vitro effects of SHBG on inflammation as well as lipid metabolism. Incubation with 20 nM SHBG markedly suppressed lipopolysaccharide- (LPS-) induced inflammatory cytokines, such as MCP-1, TNFα, and IL-6 in adipocytes and macrophages, along with phosphorylations of JNK and ERK. Anti-inflammatory effects were also observed in 3T3-L1 adipocytes cocultured with LPS-stimulated macrophages. In addition, SHBG treatment for 18 hrs or longer significantly induced the lipid degradation of differentiated 3T3-L1 cells, with alterations in its corresponding gene and protein levels. Notably, these effects of SHBG were not altered by coaddition of large amounts of testosterone or estradiol. In conclusion, SHBG suppresses inflammation and lipid accumulation in macrophages and adipocytes, which might be among the mechanisms underlying the protective effect of SHBG, that is, its actions which reduce the incidence of metabolic syndrome.http://dx.doi.org/10.1155/2018/3062319 |
| spellingShingle | Hiroki Yamazaki Akifumi Kushiyama Hideyuki Sakoda Midori Fujishiro Takeshi Yamamotoya Yusuke Nakatsu Takako Kikuchi Sunao Kaneko Hirotoshi Tanaka Tomoichiro Asano Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages Mediators of Inflammation |
| title | Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages |
| title_full | Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages |
| title_fullStr | Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages |
| title_full_unstemmed | Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages |
| title_short | Protective Effect of Sex Hormone-Binding Globulin against Metabolic Syndrome: In Vitro Evidence Showing Anti-Inflammatory and Lipolytic Effects on Adipocytes and Macrophages |
| title_sort | protective effect of sex hormone binding globulin against metabolic syndrome in vitro evidence showing anti inflammatory and lipolytic effects on adipocytes and macrophages |
| url | http://dx.doi.org/10.1155/2018/3062319 |
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