The Mechanism of Leptin on Inhibiting Fibrosis and Promoting Browning of White Fat by Reducing ITGA5 in Mice

Autor: Juntong Liang, Yizhou Li, Qiong Wu, Zhuwen Sun, Chao Sun, Yongnian Liu, Yuexia Liu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Integrins
Adipocytes
White
Adipose tissue
White adipose tissue
Wortmannin
chemistry.chemical_compound
Mice
Phosphatidylinositol 3-Kinases
Adipose Tissue
Brown
Fibrosis
Transforming Growth Factor beta
Adipocyte
Biology (General)
Spectroscopy
white fat browning
Leptin
General Medicine
Computer Science Applications
Chemistry
Adipocytes
Brown
Matrix Metalloproteinase 9
ITGA5
Signal Transduction
medicine.medical_specialty
QH301-705.5
Adipose Tissue
White
Collagen Type VI
Diet
High-Fat
adipocyte
leptin
Catalysis
Article
Collagen Type I
Inorganic Chemistry
Internal medicine
medicine
Animals
Obesity
Physical and Theoretical Chemistry
QD1-999
Molecular Biology
Protein kinase B
PI3K/AKT/mTOR pathway
Organic Chemistry
fibrosis
medicine.disease
Mice
Inbred C57BL
Endocrinology
Collagen Type III
chemistry
Gene Expression Regulation
Proto-Oncogene Proteins c-akt
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 22
International Journal of Molecular Sciences, Vol 22, Iss 12353, p 12353 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms222212353
Popis: 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.
Databáze: OpenAIRE
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