The Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice
Leptin is a small molecule protein secreted by adipocytes, which can promote white fat browning through activating the hypothalamic nervous system and inhibiting downstream signaling pathways. Moreover, white fat browning has been proven to alleviate fat tissue fibrosis. This study explores the mech...
Guardado en:
| Autores principales: | , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/d103a58d4e8f44198b68025ecdc4905b |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:d103a58d4e8f44198b68025ecdc4905b |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:d103a58d4e8f44198b68025ecdc4905b2021-11-25T17:55:41ZThe Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice10.3390/ijms2222123531422-00671661-6596https://doaj.org/article/d103a58d4e8f44198b68025ecdc4905b2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12353https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Leptin is a small molecule protein secreted by adipocytes, which can promote white fat browning through activating the hypothalamic nervous system and inhibiting downstream signaling pathways. Moreover, white fat browning has been proven to alleviate fat tissue fibrosis. This study explores the mechanism of leptin in regulating adipose tissue fibrosis and white fat browning. After treating mice with leptin, we screened out the recombinant integrin alpha 5 (ITGA5) through proteomics sequencing, which may play a role in adipose tissue fibrosis. Through real-time quantitative PCR (qPCR), western blotting (WB), hematoxylin-eosin (HE) staining, Masson’s trichrome, immunofluorescence, immunohistochemistry, etc., the results showed that after leptin treated adipocytes, the expression of fibrosis-related genes and ITGA5 was significantly down-regulated in adipocytes. We constructed fibrosis model through transforming growth factor-β (TGF-β) and a high-fat diet (HFD), and treated with ITGA5 overexpression vector and interference fragments. The results indicated the expression of fibrosis-related genes were significantly down-regulated after interfering with ITGA5. After treating adipocytes with wortmannin, fibrosis-related gene expression was inhibited after overexpression of ITGA5. Moreover, after injecting mice with leptin, we also found that leptin significantly up-regulated the expression of adipose tissue browning-related genes. Overall, our research shows that leptin can inhibit the activation of phosphatidylinositol 3 kinase (PI3K)-protein kinase B (AKT) signaling pathway by reducing the expression of ITGA5, which could alleviate adipose tissue fibrosis, and further promote white fat browning. Our research provides a theoretical basis for further research on the effect of leptin in fibrosis-related adipose tissue metabolism.Yuexia LiuYizhou LiJuntong LiangZhuwen SunQiong WuYongnian LiuChao SunMDPI AGarticleadipocyteleptinITGA5fibrosiswhite fat browningBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12353, p 12353 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
adipocyte leptin ITGA5 fibrosis white fat browning Biology (General) QH301-705.5 Chemistry QD1-999 |
| spellingShingle |
adipocyte leptin ITGA5 fibrosis white fat browning Biology (General) QH301-705.5 Chemistry QD1-999 Yuexia Liu Yizhou Li Juntong Liang Zhuwen Sun Qiong Wu Yongnian Liu Chao Sun The Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice |
| description |
Leptin is a small molecule protein secreted by adipocytes, which can promote white fat browning through activating the hypothalamic nervous system and inhibiting downstream signaling pathways. Moreover, white fat browning has been proven to alleviate fat tissue fibrosis. This study explores the mechanism of leptin in regulating adipose tissue fibrosis and white fat browning. After treating mice with leptin, we screened out the recombinant integrin alpha 5 (ITGA5) through proteomics sequencing, which may play a role in adipose tissue fibrosis. Through real-time quantitative PCR (qPCR), western blotting (WB), hematoxylin-eosin (HE) staining, Masson’s trichrome, immunofluorescence, immunohistochemistry, etc., the results showed that after leptin treated adipocytes, the expression of fibrosis-related genes and ITGA5 was significantly down-regulated in adipocytes. We constructed fibrosis model through transforming growth factor-β (TGF-β) and a high-fat diet (HFD), and treated with ITGA5 overexpression vector and interference fragments. The results indicated the expression of fibrosis-related genes were significantly down-regulated after interfering with ITGA5. After treating adipocytes with wortmannin, fibrosis-related gene expression was inhibited after overexpression of ITGA5. Moreover, after injecting mice with leptin, we also found that leptin significantly up-regulated the expression of adipose tissue browning-related genes. Overall, our research shows that leptin can inhibit the activation of phosphatidylinositol 3 kinase (PI3K)-protein kinase B (AKT) signaling pathway by reducing the expression of ITGA5, which could alleviate adipose tissue fibrosis, and further promote white fat browning. Our research provides a theoretical basis for further research on the effect of leptin in fibrosis-related adipose tissue metabolism. |
| format |
article |
| author |
Yuexia Liu Yizhou Li Juntong Liang Zhuwen Sun Qiong Wu Yongnian Liu Chao Sun |
| author_facet |
Yuexia Liu Yizhou Li Juntong Liang Zhuwen Sun Qiong Wu Yongnian Liu Chao Sun |
| author_sort |
Yuexia Liu |
| title |
The Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice |
| title_short |
The Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice |
| title_full |
The Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice |
| title_fullStr |
The Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice |
| title_full_unstemmed |
The Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice |
| title_sort |
mechanism of leptin on inhibiting fibrosis and promoting browning of white fat by reducing itga5 in mice |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/d103a58d4e8f44198b68025ecdc4905b |
| work_keys_str_mv |
AT yuexialiu themechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT yizhouli themechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT juntongliang themechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT zhuwensun themechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT qiongwu themechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT yongnianliu themechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT chaosun themechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT yuexialiu mechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT yizhouli mechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT juntongliang mechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT zhuwensun mechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT qiongwu mechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT yongnianliu mechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice AT chaosun mechanismofleptinoninhibitingfibrosisandpromotingbrowningofwhitefatbyreducingitga5inmice |
| _version_ |
1718411832667930624 |