Retinoic Acid Inhibits Adipogenesis Modulating C/EBPβ Phosphorylation and Down Regulating Srebf1a Expression.
Adipogenesis comprises a complex network of signaling pathways and transcriptional cascades; the GSK3β-C/EBPβ-srebf1a axis is a critical signaling pathway at early stages leading to the expression of PPARγ2, the master regulator of adipose differentiation. Previous work has demonstrated that retinoic acid inhibits adipogenesis affecting different signaling pathways. Here, we evaluated the anti-adipogenic effect of retinoic acid on the adipogenic transcriptional cascade, and the expression of adipogenic genes cebpb, srebf1a, srebf1c, pparg2, and cebpa. Our results demonstrate that retinoic acid blocks adipose differentiation during commitment, returning cells to an apparent non-committed state, since they have to be newly induced to adipose conversion after the retinoid is removed from the culture medium. Retinoic acid down regulates the expression of the adipogenic genes, srebf1a, srebf1c, pparg2, and cebpa; however, it did not down regulate the expression of cebpb, but it inhibited C/EBPβ phosphorylation at Thr188, a critical step for the progression of the adipogenic program. We also found that RA inhibition of adipogenesis did not increase the expression of dlk1, the gene encoding for Pref1, a well-known anti-adipogenic factor.
Instituto de Neurobiología, Universidad Nacional Autónoma de México, Blvd, Juriquilla 3001, Juriquilla, Querétaro, Mexico.
Jorge-Tonatiuh
JT
Ayala-Sumuano
Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN, Avenida Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Mexico City, Mexico.
Cristina
C
Vélez-DelValle
Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN, Avenida Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Mexico City, Mexico.
Meytha
M
Marsch-Moreno
Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN, Avenida Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Mexico City, Mexico.
Alicia
A
Beltrán-Langarica
Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN, Avenida Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Mexico City, Mexico.
Claudia
C
Hernández-Mosqueira
Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del IPN, Avenida Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Mexico City, Mexico.
Walid
W
Kuri-Harcuch
D016475:3T3 Cells; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D015536:Down-Regulation; D015870:Gene Expression; D020868:Gene Silencing; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D015398:Signal Transduction; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000494:pharmacology*
D022782:CCAAT-Enhancer-Binding Protein-beta; D002135:Calcium-Binding Proteins; C545013:Cebpb protein, mouse; C512925:Dlk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; D014212:Tretinoin
3T3-F442A; ADIPOGENESIS; C/EBPβ; SREBP1a; CELL DIFFERENTIATION; RETINOIC ACID; TRANSCRIPTIONAL CASCADE