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.
Keyphrases
- adipose tissue
- high fat diet induced
- transforming growth factor
- poor prognosis
- insulin resistance
- metabolic syndrome
- advanced non small cell lung cancer
- type diabetes
- binding protein
- cell proliferation
- recombinant human
- weight loss
- helicobacter pylori
- gene expression
- protein kinase
- dna methylation
- body mass index
- protein protein
- oxidative stress
- small molecule
- high glucose
- epidermal growth factor receptor
- drug induced
- tyrosine kinase
- fatty acid