scholarly journals A Role for PPARβ/δin Tumor Stroma and Tumorigenesis

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-5 ◽  
Author(s):  
Rolf Müller ◽  
Martin Kömhoff ◽  
Jeffrey M. Peters ◽  
Sabine Müller-Brüsselbach

Peroxisome proliferator-activated receptor-β/δ(PPARβ/δ) is a transcription factor that is activated by endogenous fatty acid ligands and by synthetic agonists. Its role in the regulation of skeletal muscle fatty acid catabolism, glucose homeostasis, and cellular differentiation has been established in multiple studies. On the contrary, a role for PPARβ/δin tumorigenesis is less clear because there are contradictory reports in the literature. However, the majority of these studies have not examined the role of PPARβ/δin the tumor stroma. Recent evidence suggests that stromal PPARβ/δregulates tumor endothelial cell proliferation and promotes differentiation leading to the properly orchestrated events required for tumor blood vessel formation. This review briefly summarizes the significance of these studies that may provide clues to help explain the reported discrepancies in the literature regarding the role of PPARβ/δin tumorigenesis.

2020 ◽  
Vol 21 (6) ◽  
pp. 2061 ◽  
Author(s):  
Yaping Wang ◽  
Takero Nakajima ◽  
Frank J. Gonzalez ◽  
Naoki Tanaka

Peroxisome proliferator-activated receptor (PPAR) α, β/δ, and γ modulate lipid homeostasis. PPARα regulates lipid metabolism in the liver, the organ that largely controls whole-body nutrient/energy homeostasis, and its abnormalities may lead to hepatic steatosis, steatohepatitis, steatofibrosis, and liver cancer. PPARβ/δ promotes fatty acid β-oxidation largely in extrahepatic organs, and PPARγ stores triacylglycerol in adipocytes. Investigations using liver-specific PPAR-disrupted mice have revealed major but distinct contributions of the three PPARs in the liver. This review summarizes the findings of liver-specific PPAR-null mice and discusses the role of PPARs in the liver.


Biochimie ◽  
2004 ◽  
Vol 86 (11) ◽  
pp. 833-837 ◽  
Author(s):  
Serge Luquet ◽  
Joaquin Lopez-Soriano ◽  
Dorte Holst ◽  
Céline Gaudel ◽  
Chantal Jehl-Pietri ◽  
...  

2020 ◽  
Vol 21 (12) ◽  
pp. 4403 ◽  
Author(s):  
Sze Yuan Ho ◽  
Yuet Ping Kwan ◽  
Beiying Qiu ◽  
Alison Tan ◽  
Hannah Louise Murray ◽  
...  

Peroxisome proliferator-activated receptor (PPAR)β/δ is a member of the nuclear receptor superfamily of transcription factors, which plays fundamental roles in cell proliferation and differentiation, inflammation, adipogenesis, and energy homeostasis. Previous studies demonstrated a reduced choroidal neovascularization (CNV) in Pparβ/δ-deficient mice. However, PPARβ/δ’s role in physiological blood vessel formation and vessel remodeling in the retina has yet to be established. Our study showed that PPARβ/δ is specifically required for disordered blood vessel formation in the retina. We further demonstrated an increased arteriovenous crossover and wider venous caliber in Pparβ/δ-haplodeficient mice. In summary, these results indicated a critical role of PPARβ/δ in pathological angiogenesis and blood vessel remodeling in the retina.


2018 ◽  
Vol 217 (4) ◽  
pp. 1353-1368 ◽  
Author(s):  
Laura Montani ◽  
Jorge A. Pereira ◽  
Camilla Norrmén ◽  
Hartmut B.F. Pohl ◽  
Elisa Tinelli ◽  
...  

Myelination calls for a remarkable surge in cell metabolism to facilitate lipid and membrane production. Endogenous fatty acid (FA) synthesis represents a potentially critical process in myelinating glia. Using genetically modified mice, we show that Schwann cell (SC) intrinsic activity of the enzyme essential for de novo FA synthesis, fatty acid synthase (FASN), is crucial for precise lipid composition of peripheral nerves and fundamental for the correct onset of myelination and proper myelin growth. Upon FASN depletion in SCs, epineurial adipocytes undergo lipolysis, suggestive of a compensatory role. Mechanistically, we found that a lack of FASN in SCs leads to an impairment of the peroxisome proliferator-activated receptor (PPAR) γ–regulated transcriptional program. In agreement, defects in myelination of FASN-deficient SCs could be ameliorated by treatment with the PPARγ agonist rosiglitazone ex vivo and in vivo. Our results reveal that FASN-driven de novo FA synthesis in SCs is mandatory for myelination and identify lipogenic activation of the PPARγ transcriptional network as a putative downstream functional mediator.


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