Abstract
Preadipocyte factor 1 (Pref-1, also called Dlk1/FA1) is a molecular gatekeeper of adipogenesis which acts by maintaining the preadipocyte state and preventing adipocyte differentiation. Pref-1 is made as an epidermal growth factor-like repeat containing transmembrane protein, and is cleaved by TNFα-converting enzyme (TACE) to generate a soluble form, which acts as an autocrine/paracrine factor. Pref-1 upregulates Sox9 expression by activating the ERK/MAPK pathway and the Pref-1 interaction with fibronectin is required for inhibition of adipogenesis. Pref-1 also prevents brown adipocyte differentiation and its thermogenic function. Here, we highlight the recent evidence for the role of Pref-1 in adipogenesis.
Highlights
With the recent evidence of the presence of functional brown adipose tissue (BAT) in adults, implicating its potential as a therapeutic target for obesity, attention has been focused on understanding the development of BAT, which dissipates energy, in contrast to white adipose tissue (WAT) that serves as the major energy storage organ
We originally identified Preadipocyte factor-1 [Pref-1; called Dlk1 (Delta-like protein-1), fetal antigen-1 (FA1)] as a preadipocyte factor that prevents adipocyte differentiation and Pref-1 expression is decreased during differentiation to allow adipogenesis [14,15,16]
Pref-1 has been used as a preadipocyte marker, and is notable in its ability to prevent adipocyte differentiation in an autocrine/paracrine manner
Summary
Is enhanced by phorbol ester treatment, showing that Protein Kinase C may regulate Pref-1 cleavage. We found that knockdown of fibronectin or addition of Pref-1 interacting domains of fibronectin prevent the Pref-1 mediated activation of MEK/ERK and Sox induction, resulting in enhancement of adipocyte differentiation. An indirect mechanism of this effect may be through the DEX-mediated induction of C/EPBδ, as was recently demonstrated by Armengol et al [32] Taken together, these results demonstrate that Pref-1 plays an important role in the regulation of both WAT and BAT differentiation. The Pref-1 level was increased at the commitment stage, indicating that epinephrine may induce cells to become committed to the adipocyte lineage This effect could be reversed by treatment with antagonists of the Neuropeptide Y (NPY) receptor [36].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
