| RRC ID |
82842
|
| Author |
Sakaki M, Kamatari Y, Kurisaki A, Funaba M, Hashimoto O.
|
| Title |
Activin E upregulates uncoupling protein 1 and fibroblast growth factor 21 in brown adipocytes.
|
| Journal |
Mol Cell Endocrinol
|
| Abstract |
Activin E activates brown and beige adipocytes and has been controversially implicated as a factor that induces obesity and fatty liver. Here, we sought to address this controversial issue by producing recombinant human activin E to evaluate its effects on HB2 brown adipocytes in vitro. Activin E increased uncoupling protein 1 (Ucp1) and fibroblast growth factor 21 (Fgf21) mRNA expression in the adipocytes. This upregulation was suppressed by SB431542, an inhibitor of activin receptor-like kinase (Alk) TGF-β type I receptors. SB431542 also inhibited the activin E-induced phosphorylation of Smad2/3. A promoter assay using a CAGA-Luc reporter and Alk expression vectors revealed that activin E activated the TGF-β/activin pathway via Alk7. The upregulation of Ucp1 and Fgf21 mRNA might be mediated through Alk7 and Smad2/3 phosphorylation. Activin E is a potential stimulator of energy expenditure by activating brown adipocytes and highlights its potential as a therapeutic target for treating obesity.
|
| Volume |
592
|
| Pages |
112326
|
| Published |
2024-10-1
|
| DOI |
10.1016/j.mce.2024.112326
|
| PII |
S0303-7207(24)00182-5
|
| PMID |
38972346
|
| MeSH |
Activin Receptors, Type I* / genetics
Activin Receptors, Type I* / metabolism
Activins* / metabolism
Adipocytes, Brown* / drug effects
Adipocytes, Brown* / metabolism
Benzamides
Cell Line
Dioxoles* / pharmacology
Fibroblast Growth Factors* / genetics
Fibroblast Growth Factors* / metabolism
Humans
Phosphorylation / drug effects
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptor, Transforming Growth Factor-beta Type I / genetics
Receptor, Transforming Growth Factor-beta Type I / metabolism
Recombinant Proteins / metabolism
Recombinant Proteins / pharmacology
Signal Transduction / drug effects
Smad2 Protein / genetics
Smad2 Protein / metabolism
Smad3 Protein / genetics
Smad3 Protein / metabolism
Uncoupling Protein 1* / genetics
Uncoupling Protein 1* / metabolism
Up-Regulation* / drug effects
|
| IF |
3.871
|
| Resource |
| Human and Animal Cells |
Hep G2 |
