Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in mice
Objective: Long-term glucocorticoids (GCs) therapy usually causes many metabolic side effects, including fatty liver. However, the molecular mechanisms remain poorly understood. Herein, we explored the molecular basis of GCs in the development of fatty liver. Methods: C57BL/6 male mice were injected...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | Molecular Metabolism |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877819309305 |
| _version_ | 1818504669921542144 |
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| author | Jian Wan Yi Shan Xi Song Song Chen Xinyuan Lu Jie Jin Qing Su Bin Liu Wanju Sun Bo Li |
| author_facet | Jian Wan Yi Shan Xi Song Song Chen Xinyuan Lu Jie Jin Qing Su Bin Liu Wanju Sun Bo Li |
| author_sort | Jian Wan |
| collection | DOAJ |
| description | Objective: Long-term glucocorticoids (GCs) therapy usually causes many metabolic side effects, including fatty liver. However, the molecular mechanisms remain poorly understood. Herein, we explored the molecular basis of GCs in the development of fatty liver. Methods: C57BL/6 male mice were injected with Dexamethasone (DEX) while mouse primary hepatocytes (MPHs), HepG2 and Hep1-6 cells were cultured in the presence of DEX. Genes expression in liver tissues and hepatocytes were assessed by quantitative real-time PCR and western blotting, respectively. To explore whether Periostin is involved in the development of GCs-induced fatty liver, wild-type and Periostin knockout mice were treated with DEX or vehicle control. Luciferase reporter and chromatin immunoprecipitation assays were used to determine the regulatory roles of GCs on Periostin expression. Results: We show that treatment of dexamethasone (DEX), a synthetic analog of GCs, led to the accumulation of triglycerides in the livers of mice, but not in cultured hepatocytes, suggesting that GCs may promote liver steatosis through integrative organ crosstalk mediated by systemic factors. We further found that DEX upregulated the expression levels of Periostin in white adipose tissues, which in turn promoted liver steatosis. Administration of a Periostin-neutralizing antibody or genetic ablation of Periostin largely attenuated DEX-induced hepatic steatosis in mice. Conclusions: Our findings provided a novel insight that GCs could promote liver steatosis through integrative organ crosstalk mediated by white fat-secreted Periostin. These results establish Periostin as an endocrine factor with therapeutic potential for the treatment of GCs-associated fatty liver. Keywords: Periostin, Glucocorticoid, Fatty liver, Adipocyte, Hyperglycemia |
| first_indexed | 2024-12-10T21:40:12Z |
| format | Article |
| id | doaj.art-defa4d7f168c41ae9ebb6526fabc9ab5 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-10T21:40:12Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-defa4d7f168c41ae9ebb6526fabc9ab52022-12-22T01:32:32ZengElsevierMolecular Metabolism2212-87782020-01-01312435Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in miceJian Wan0Yi Shan1Xi Song2Song Chen3Xinyuan Lu4Jie Jin5Qing Su6Bin Liu7Wanju Sun8Bo Li9Department of Emergency and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201299, ChinaDepartment of Emergency and ICU, Changzheng Hospital, Second Military Medical University, Shanghai 200003, ChinaDepartment of Emergency and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201299, ChinaDepartment of Emergency and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201299, ChinaDepartment of Emergency and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201299, ChinaDepartment of Endocrinology, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaDepartment of Endocrinology, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, ChinaHubei Key Laboratory for Kidney Disease Pathogenesis and Intervention, Hubei Polytechnic University School of Medicine, Huangshi, Hubei 435003, ChinaDepartment of Emergency and Critical Care Medicine, Shanghai Pudong New Area People's Hospital, Shanghai University of Medicine and Health Sciences, Shanghai 201299, China; Corresponding author. Department of Emergency and Trauma Centre, Pudong New Area People's Hospital, Shanghai 201299, China Tel.: +86 21 20509287.Department of Endocrinology, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Corresponding author. Department of Endocrinology, XinHua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China Tel.: +86 21 65790000 ext. 537535.Objective: Long-term glucocorticoids (GCs) therapy usually causes many metabolic side effects, including fatty liver. However, the molecular mechanisms remain poorly understood. Herein, we explored the molecular basis of GCs in the development of fatty liver. Methods: C57BL/6 male mice were injected with Dexamethasone (DEX) while mouse primary hepatocytes (MPHs), HepG2 and Hep1-6 cells were cultured in the presence of DEX. Genes expression in liver tissues and hepatocytes were assessed by quantitative real-time PCR and western blotting, respectively. To explore whether Periostin is involved in the development of GCs-induced fatty liver, wild-type and Periostin knockout mice were treated with DEX or vehicle control. Luciferase reporter and chromatin immunoprecipitation assays were used to determine the regulatory roles of GCs on Periostin expression. Results: We show that treatment of dexamethasone (DEX), a synthetic analog of GCs, led to the accumulation of triglycerides in the livers of mice, but not in cultured hepatocytes, suggesting that GCs may promote liver steatosis through integrative organ crosstalk mediated by systemic factors. We further found that DEX upregulated the expression levels of Periostin in white adipose tissues, which in turn promoted liver steatosis. Administration of a Periostin-neutralizing antibody or genetic ablation of Periostin largely attenuated DEX-induced hepatic steatosis in mice. Conclusions: Our findings provided a novel insight that GCs could promote liver steatosis through integrative organ crosstalk mediated by white fat-secreted Periostin. These results establish Periostin as an endocrine factor with therapeutic potential for the treatment of GCs-associated fatty liver. Keywords: Periostin, Glucocorticoid, Fatty liver, Adipocyte, Hyperglycemiahttp://www.sciencedirect.com/science/article/pii/S2212877819309305 |
| spellingShingle | Jian Wan Yi Shan Xi Song Song Chen Xinyuan Lu Jie Jin Qing Su Bin Liu Wanju Sun Bo Li Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in mice Molecular Metabolism |
| title | Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in mice |
| title_full | Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in mice |
| title_fullStr | Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in mice |
| title_full_unstemmed | Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in mice |
| title_short | Adipocyte-derived Periostin mediates glucocorticoid-induced hepatosteatosis in mice |
| title_sort | adipocyte derived periostin mediates glucocorticoid induced hepatosteatosis in mice |
| url | http://www.sciencedirect.com/science/article/pii/S2212877819309305 |
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