Adult Cartilage-Specific Peroxisome Proliferator–Activated Receptor Gamma Knockout Mice Exhibit the Spontaneous Osteoarthritis Phenotype

2013 ◽  
Vol 182 (4) ◽  
pp. 1099-1106 ◽  
Author(s):  
Faezeh Vasheghani ◽  
Roxana Monemdjou ◽  
Hassan Fahmi ◽  
Yue Zhang ◽  
Gemma Perez ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Role of peroxisome proliferator-activated receptor-α in ileum tight junction alteration in mouse model of restraint stress

2009 ◽  
Vol 297 (3) ◽  
pp. G488-G505 ◽  
Author(s):  
Emanuela Mazzon ◽  
Concetta Crisafulli ◽  
Maria Galuppo ◽  
Salvatore Cuzzocrea
Keyword(s):  
Tight Junction ◽  
Knockout Mice ◽  
Restraint Stress ◽  
Immobilization Stress ◽  
Peroxisome Proliferator ◽  
Barrier Dysfunction ◽  
Peroxisome Proliferator Activated Receptor ◽  
Significant Augmentation ◽  
Tight Junction Permeability

Restraint stress induces permeability changes in the small intestine, but little is known about the role of endogenous peroxisome proliferator-activated receptor-α (PPAR-α) ligand in the defects of the tight junction function. In the present study, we used PPAR-α knockout mice to understand the roles of endogenous PPAR-α on ileum altered permeability function in models of immobilization stress. The absence of a functional PPAR-α gene in PPAR-α knockout mice resulted in a significant augmentation of the degree of 1) TNF-α production in ileum tissues; 2) the alteration of zonula occludens-1, occludin, and β-catenin (immunohistochemistry); and 3) apoptosis (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that endogenous PPAR-α ligands reduce the degree of tight junction permeability in the ileum tissues associated with immobilization stress, suggesting a possible role of endogenous PPAR-α ligands on ileum barrier dysfunction.

scholarly journals PPARg Dysfunction in the Medial Prefrontal Cortex Mediates High-Fat Diet-Induced Depression

2021 ◽  
Author(s):  
Cong-Cong Fu ◽  
Xin-Yi Zhang ◽  
Liu Xu ◽  
Hui-Xian Huang ◽  
Shuang Xu ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
High Fat ◽  
Peroxisome Proliferator Activated Receptor ◽  
Increased Risk ◽  
Bidirectional Association

Abstract ObjectiveEpidemiological studies suggest a bidirectional association between depression and obesity; however, the biological mechanisms that link the development of depression to a metabolic disorder remain unclear. Even though nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) agonists show anti-depressive effect, and high-fat diet-(HFD)-induced PPARγ dysfunction is involved in the pathogenesis of metabolic disorders, the neuronal PPARg has never been studied in HFD-induced depression. Thus, we aimed to investigate the effect of neuronal PPARγ on depressive-like behaviors in HFD-induced obese mice. MethodsWe fed male C57BL/6J mice with HFD to generate obese mice and conducted a series of behavioral tests to assess the effects of HFD feeding on depression. We generated neuron-specific PPARγ knockout mice (NKO) to determine whether neuronal PPARg deficiency was correlated with depressive-like behaviors. To further prove whether PPARγ in the medial prefrontal cortex (mPFC) neurons is involved in depressive-like behaviors, we applied AAV- CaMKIIa-Cre approach to specifically knockout PPARγ in the mPFC neurons of LoxP mice and used AAV-syn-PPARγ vectors to overexpress PPARγ in the mPFC neurons of NKO mice. ResultsWe observed a low mPFC PPARγ level and an increase in depressive-like behaviors in the HFD-fed mice. Moreover, neuronal-specific PPARγ deficiency in mice induced depressive-like behaviors, which could be abolished by imipramine. Furthermore, overexpressing PPARg in the mPFC reversed the depressive-like behaviors in HFD-fed mice as well as in neuronal-specific PPARγ knockout mice. ConclusionsThese results implicate that dysregulation of neuronal PPARγ in the mPFC may contribute to an increased risk for depression in obese populations.

scholarly journals PPAR-α Deletion Attenuates Cisplatin Nephrotoxicity by Modulating Renal Organic Transporters MATE-1 and OCT-2

2020 ◽  
Vol 21 (19) ◽  
pp. 7416
Author(s):  
Leandro Ceotto Freitas-Lima ◽  
Alexandre Budu ◽  
Adriano Cleis Arruda ◽  
Mauro Sérgio Perilhão ◽  
Jonatan Barrera-Chimal ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Renal Damage ◽  
Peroxisome Proliferator ◽  
Tubular Injury ◽  
Wild Type ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cisplatin Nephrotoxicity ◽  
Main Protein ◽  
First Time ◽  
Cisplatin Therapy

Cisplatin is a chemotherapy drug widely used in the treatment of solid tumors. However, nephrotoxicity has been reported in about one-third of patients undergoing cisplatin therapy. Proximal tubules are the main target of cisplatin toxicity and cellular uptake; elimination of this drug can modulate renal damage. Organic transporters play an important role in the transport of cisplatin into the kidney and organic cations transporter 2 (OCT-2) has been shown to be one of the most important transporters to play this role. On the other hand, multidrug and toxin extrusion 1 (MATE-1) transporter is the main protein that mediates the extrusion of cisplatin into the urine. Cisplatin nephrotoxicity has been shown to be enhanced by increased OCT-2 and/or reduced MATE-1 activity. Peroxisome proliferator-activated receptor alpha (PPAR-α) is the transcription factor which controls lipid metabolism and glucose homeostasis; it is highly expressed in the kidneys and interacts with both MATE-1 and OCT-2. Considering the above, we treated wild-type and PPAR-α knockout mice with cisplatin in order to evaluate the severity of nephrotoxicity. Cisplatin induced renal dysfunction, renal inflammation, apoptosis and tubular injury in wild-type mice, whereas PPAR-α deletion protected against these alterations. Moreover, we observed that cisplatin induced down-regulation of organic transporters MATE-1 and OCT-2 and that PPAR-α deletion restored the expression of these transporters. In addition, PPAR-α knockout mice at basal state showed increased MATE-1 expression and reduced OCT-2 levels. Here, we show for the first time that PPAR-α deletion protects against cisplatin nephrotoxicity and that this protection is via modulation of the organic transporters MATE-1 and OCT-2.

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