| First Author | Lee ES | Year | 2023 |
| Journal | J Biol Chem | Volume | 299 |
| Issue | 1 | Pages | 102716 |
| PubMed ID | 36403856 | Mgi Jnum | J:351108 |
| Mgi Id | MGI:7412264 | Doi | 10.1016/j.jbc.2022.102716 |
| Citation | Lee ES, et al. (2022) Activin receptor ALK4 promotes adipose tissue hyperplasia by suppressing differentiation of adipocyte precursors. J Biol Chem 299(1):102716 |
| abstractText | Adipocyte hyperplasia and hypertrophy are the two main processes contributing to adipose tissue expansion, yet the mechanisms that regulate and balance their involvement in obesity are incompletely understood. Activin B/GDF-3 receptor ALK7 is expressed in mature adipocytes and promotes adipocyte hypertrophy upon nutrient overload by suppressing adrenergic signaling and lipolysis. In contrast, the role of ALK4, the canonical pan-activin receptor, in adipose tissue is unknown. Here, we report that, unlike ALK7, ALK4 is preferentially expressed in adipocyte precursors, where it suppresses differentiation, allowing proliferation and adipose tissue expansion. ALK4 expression in adipose tissue increases upon nutrient overload and positively correlates with fat depot mass and body weight, suggesting a role in adipose tissue hyperplasia during obesity. Mechanistically, ALK4 signaling suppresses expression of CEBPalpha and PPARgamma, two master regulators of adipocyte differentiation. Conversely, ALK4 deletion enhances CEBPalpha/PPARgamma expression and induces premature adipocyte differentiation, which can be rescued by CEBPalpha knockdown. These results clarify the function of ALK4 in adipose tissue and highlight the contrasting roles of the two activin receptors in the regulation of adipocyte hyperplasia and hypertrophy during obesity. |
