C/EBPalpha induces adipogenesis through PPARgamma: a unified pathway.

By E. Rosen, Chung-Hsin Hsu, Xinzhong Wang, S. Sakai, M. Freeman, F. Gonzalez, B. Spiegelman. Genes & Development, 2002

1,436 citations recorded by the source corpus.

PPARgamma and C/EBPalpha are critical transcription factors in adipogenesis, but the precise role of these proteins has been difficult to ascertain because they positively regulate each other's expression. Questions remain about whether these factors operate independently in separate, parallel pathways of differentiation, or whether a single pathway exists. PPARgamma can promote adipogenesis in C/EBPalpha-deficient cells, but the converse has not been tested. We have created an immortalized line of fibroblasts lacking PPARgamma, which we use to show that C/EBPalpha has no ability to promote adipogenesis in the absence of PPARgamma. These results indicate that C/EBPalpha and PPARgamma participate in a single pathway of fat cell development with PPARgamma being the proximal effector of adipogenesis.

Subfields: Epidemiology, Molecular Biology, Physiology

View Paper: https://www.semanticscholar.org/paper/3b52b5e6348c8e8403204dc468e4b0fc2d59fc7d

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Epidemiology

1. B. Spiegelman
2. E. Rosen
3. S. Kajimura
4. P. Seale
5. Jiandie D. Lin
6. G. Hotamışlıgil
7. Haiming Cao
8. Liangyou Rui

In Molecular Biology

1. B. Spiegelman
2. E. Rosen
3. P. Seale
4. S. Kajimura
5. Jiandie D. Lin
6. Wenli Yang
7. Marc Uldry
8. J. St-Pierre

In Physiology

1. B. Spiegelman
2. S. Kajimura
3. P. Seale
4. E. Rosen
5. S. Farmer
6. Wenli Yang
7. Jiandie D. Lin
8. Marc Uldry

Citations in the corpus

• Liver-specific disruption of PPARgamma in leptin-deficient mice improves fatty liver but aggravates diabetic phenotypes. (2003, background): “Immortalized fibroblasts lacking PPARγ lose the potential for differentiation to mature adipocytes (3), indicating that PPARγ is absolutely required for differentiation of preadipocytes to mature adipocytes.”
• The role of Peroxisome Proliferator-Activated Receptors (PPAR) in immune responses (2020, background): “Similarly, mice with PPARγ ablation failed to develop all types of fat [28,29].”
• Transcriptional control of adipocyte formation. (2006, background): “PPARg in particular is considered the master regulator of adipogenesis; without it, precursor cells are incapable of expressing any known aspect of the adipocyte phenotype (Rosen et al., 2002).”
• Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. (2003, background): “There is reciprocal regulation of PPAR and C/EBP , and it was shown that deletion of PPAR reduces C/EBP expression following induction of differentiation (Rosen et al. 2002).”
• Transcriptional control of adipose lipid handling by IRF4 (2011, methodology): “Primary MEFs were generated and plated as monolayer cultures in DMEM with 10% FBS as described previously (Rosen et al., 2002).”
• Complementary action of the PGC-1 coactivators in mitochondrial biogenesis and brown fat differentiation. (2006, background): “…biogenesis and brown fat differentiation Marc Uldry,1 Wenli Yang,1 Julie St-Pierre,1 Jiandie Lin,1 Patrick Seale,1 and Bruce M. Spiegelman1,* 1Dana-Farber Cancer Institute, Harvard Medical School, 1 Jimmy Fund Way, Boston, Massachusetts 02115 *Correspondence: bruce_spiegelman@dfci.harvard.edu”
• What We Talk About When We Talk About Fat (2014, positive): “Differentiation is ‘‘locked in’’ by a positive feedback loop between PPARg and C/EBPa (Rosen et al., 2002; Wu et al., 1999); a second positive feedback loop between PPARg and C/EBPb reinforces the decision to differentiate (Park et al.”
• Obesity-linked phosphorylation of PPARγ by cdk5 is a direct target of the anti-diabetic PPARγ ligands (2010, neutral): “4a)21.”
• Transcriptional control of brown fat determination by PRDM16. (2007, background): “To study its role in brown fat cells, we first expressed PRDM16 in cells with no preadipose (white or brown) character whatsoever, using fibroblasts genetically deficient in PPARγ (Rosen et al., 2002).”