FGF9 inhibits browning program of white adipocytes and associates with human obesity
| Autor: | Weiqing Wang, Lingyun Tang, Zhugang Wang, Jie Hong, Guang Ning, Yingkai Sun, Rui Wang, Ruixin Liu, Jiqiu Wang, Wen Liu, Wen Li, Shaoqian Zhao |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Fibroblast Growth Factor 9 Male 0301 basic medicine medicine.medical_specialty FGF21 Adolescent Adipose Tissue White Adipocytes White Adipose tissue White adipose tissue Biology Fibroblast growth factor Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Adipose Tissue Brown Internal medicine Adipocyte medicine Animals Humans Obesity RNA Messenger Molecular Biology Gene knockdown Cell Differentiation Thermogenesis Stromal vascular fraction Hypoxia-Inducible Factor 1 alpha Subunit Mice Inbred C57BL stomatognathic diseases 030104 developmental biology Gene Expression Regulation chemistry Female 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Journal of Molecular Endocrinology. 62:79-90 |
| ISSN: | 1479-6813 0952-5041 |
| Popis: | Browning of white adipose tissue has been proven to be a potential target to fight against obesity and its metabolic commodities, making the exploration of molecules involved in browning process important. Among those browning agents reported recently, FGF21 play as a quite promising candidate for treating obesity for its obvious enhancement of thermogenic capacity in adipocyte and significant improvement of metabolic disorders in both mice and human. However, whether other members of fibroblast growth factor (FGF) family play roles in adipose thermogenesis and obese development is still an open question. Here, we examined the mRNA expression of all FGF family members in three adipose tissues of male C57BL/6 mice and found that FGF9 is highly expressed in adipose tissue and decreased under cold stress. Furthermore, FGF9 treatment inhibited thermogenic genes in the process of beige adipocytes differentiation from stromal vascular fraction (SVF) in a dose-dependent manner. Similar results were obtained with FGF9 overexpression. Consistently, knockdown of FGF9 in SVF cells by using lentiviral shRNA increased thermogenic genes in differentiated beige adipocytes. RNA sequencing analysis revealed a significant increment of hypoxia-inducible factor (HIF) pathway in the early stage of beige adipocytes differentiation under FGF9 treatment, which was validated by real-time PCR. FGF9 expression was increased in subcutaneous WAT of obese human and mice. This study shows that adipose-derived FGF9 play as an inhibitory role in the browning of white adipocytes. Activation of hypoxia signaling at early stage of adipose browning process may contribute to this anti-thermogenic effect of FGF9. |
| Databáze: | OpenAIRE |
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