scholarly journals PPAR-γ Agonists and Their Role in Primary Cicatricial Alopecia

PPAR Research ◽  
2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Sarawin Harnchoowong ◽  
Poonkiat Suchonwanit
Keyword(s):  
Clinical Trials ◽  
Review Article ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Biogenesis ◽  
Sebaceous Glands ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lichen Planopilaris ◽  
Ppar Γ ◽  
Ppar Agonists

Peroxisome proliferator-activated receptor γ (PPAR-γ) is a ligand-activated nuclear receptor that regulates the transcription of various genes. PPAR-γ plays roles in lipid homeostasis, sebocyte maturation, and peroxisome biogenesis and has shown anti-inflammatory effects. PPAR-γ is highly expressed in human sebaceous glands. Disruption of PPAR-γ is believed to be one of the mechanisms of primary cicatricial alopecia (PCA) pathogenesis, causing pilosebaceous dysfunction leading to follicular inflammation. In this review article, we discuss the pathogenesis of PCA with a focus on PPAR-γ involvement in pathogenesis of lichen planopilaris (LPP), the most common lymphocytic form of PCA. We also discuss clinical trials utilizing PPAR-agonists in PCA treatment.

scholarly journals PPAR Agonist-Mediated Protection against HIV Tat-Induced Cerebrovascular Toxicity is Enhanced in MMP-9-Deficient Mice

2014 ◽  
Vol 34 (4) ◽  
pp. 646-653 ◽  
Author(s):  
Wen Huang ◽  
Lei Chen ◽  
Bei Zhang ◽  
Minseon Park ◽  
Michal Toborek
Keyword(s):  
Neuronal Loss ◽  
Specific Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Brain Infection ◽  
Ppar Γ ◽  
Ppar Agonists ◽  
Bbb Permeability ◽  
Deficient Mice ◽  
Hiv 1

The strategies to protect against the disrupted blood–brain barrier (BBB) in HIV-1 infection are not well developed. Therefore, we investigated the potential of peroxisome proliferator-activated receptor (PPAR) agonists to prevent enhanced BBB permeability induced by HIV-1-specific protein Tat. Exposure to Tat via the internal carotid artery (ICA) disrupted permeability across the BBB; however, this effect was attenuated in mice treated with fenofibrate (PPAR α agonist) or rosiglitazone (PPAR γ agonist). In contrast, exposure to GW9662 (PPAR γ antagonist) exacerbated Tat-induced disruption of the BBB integrity. Increased BBB permeability was associated with decreased tight junction (TJ) protein expression and activation of ERK1/2 and Akt in brain microvessels; these effects were attenuated by cotreatment with fenofibrate but not with rosiglitazone. Importantly, both PPAR agonists also protected against Tat-induced astrogliosis and neuronal loss. Because disruption of TJ integrity has been linked to matrix metalloproteinase (MMP) activity, we also evaluated Tat-induced effects in MMP-9-deficient mice. Tat-induced cerebrovascular toxicity, astrogliosis, and neuronal loss were less pronounced in MMP-9-deficient mice as compared with wild-type controls and were further attenuated by PPAR agonists. These results indicate that enhancing PPAR activity combined with targeting MMPs may provide effective therapeutic strategies in brain infection by HIV-1.

Use of Pioglitazone in Patients with Lichen Planopilaris

2012 ◽  
Vol 16 (2) ◽  
pp. 97-100 ◽  
Author(s):  
Akerke Baibergenova ◽  
Scott Walsh
Keyword(s):  
Side Effects ◽  
Science Research ◽  
Tissue Expression ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Lichen Planopilaris ◽  
Ppar Γ ◽  
Pparγ Agonists ◽  
Left Calf ◽  
Calf Pain

Background: Recent basic science research has revealed a decreased tissue expression of peroxisome proliferator-activated receptor (PPAR) γ in lichen planopilaris (LPP). Therefore, thiazolidinediones, being PPARγ agonists, could be used to treat LPP. Methods: We followed 24 patients with LPP who were treated with oral pioglitazone hydrochloride. Improvement in LPP was defined as a decrease in or disappearance of symptoms and perifollicular erythema in the context of halted spread of old patches. Results: Twenty of 24 patients were females. The average age was 52.5 years, and ages ranged from 22 to 70 years. Five of 24 patients have achieved remission; improvement was noted in half of the patients; there was no change in 3 patients; and 4 patients discontinued treatment due to side effects. Side effects were mild and included left calf pain, lightheadedness and nausea, dizziness, and hives. Conclusion: Use of thiazolidinediones might be a new promising venue of LPP treatment.

Ciglitazone Inhibits Plasmin-Induced Proinflammatory Monocyte Activation via Modulation of p38 MAP Kinase Activity

2002 ◽  
Vol 88 (08) ◽  
pp. 274-281 ◽  
Author(s):  
Tatiana Syrovets ◽  
Almut Schüle ◽  
Marina Jendrach ◽  
Berthold Büchele ◽  
Thomas Simmet
Keyword(s):  
Gene Activation ◽  
P38 Map Kinase ◽  
Clofibric Acid ◽  
Peroxisome Proliferator ◽  
Surface Plasmon Resonance Analysis ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Pparγ Agonist ◽  
Tnf Α ◽  
Ppar Agonists

SummaryPlasmin triggers chemotaxis and NF-κBand AP-1-mediated proinflammatory gene expression in human peripheral monocytes (PM). Compared with macrophages and dendritic cells, PM express mainly the peroxisome proliferator-activated receptor (PPAR) γ and traces of PPARα as detected by semiquantitative RT-PCR and immunoblotting. The PPARγ agonist ciglitazone, but not the PPARα agonist clofibric acid, concentration-dependently inhibited the plasmin-, but not the FMLP-induced PM chemotaxis. Similarly, release of interleukin (IL)-1α, IL-1β and tumor necrosis factor (TNF)-α from plasmin-stimulated PM was concentration-dependently inhibited by ciglitazone, but not by clofibric acid, while the LPS-induced TNF-α release remained unaffected by any of both PPAR agonists. Ciglitazone activates PPARγ as shown by a novel surface plasmon resonance analysis and inhibits the plasmin-induced activation of NF-κB and AP-1. It also inhibits p38 MAPK phosphorylation essential for the plasmin-induced PM chemotaxis and gene activation. Thus, activation of PPARγ by ciglitazone may allow controling of the plasmin-mediated recruitment and activation of PM at sites of inflammation.

Mechanism of constrictive vascular remodeling by homocysteine: role of PPAR

2002 ◽  
Vol 282 (5) ◽  
pp. C1009-C1015 ◽  
Author(s):  
Vibhas S. Mujumdar ◽  
Chandra M. Tummalapalli ◽  
Giorgio M. Aru ◽  
Suresh C. Tyagi
Keyword(s):  
Endothelial Cells ◽  
Vascular Remodeling ◽  
Peroxisome Proliferator ◽  
Collagen Gels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Aortic Endothelial Cells ◽  
Ppar Γ ◽  
Collagen Contraction ◽  
Ppar Agonists

To test the hypothesis that homocysteine induces constrictive vascular remodeling by inactivating peroxisome proliferator-activated receptor (PPAR), aortic endothelial cells (ECs) and smooth muscle cells (SMCs) were isolated. Collagen gels were prepared, and ECs or SMCs (105) or SMCs + ECs (104) were incorporated into the gels. To characterize PPAR, agonists of PPAR-α [ciprofibrate (CF)] and PPAR-γ [15-deoxy-12,14-prostaglandin J2 (PGJ2)] were used. To determine the role of disintegrin metalloproteinase (DMP), cardiac inhibitor of metalloproteinase (CIMP) was used in collagen gels. Gel diameter at 0 h was 14.1 ± 0.2 mm and was unchanged up to 24 h as measured by a digital micrometer. SMCs reduce gel diameter to 10.5 ± 0.4 mm at 24 h. Addition of homocysteine to SMCs reduces further the gel diameter to 8.0 ± 0.2 mm, suggesting that SMCs induce contraction and that the contraction is further enhanced by homocysteine. Addition of ECs and SMCs reduces gel diameter to 12.0 ± 0.3 mm, suggesting that ECs play a role in collagen contraction. Only PGJ2, not CF, inhibits SMC contraction. However, both PGJ2 and CF inhibit contraction of ECs and SMCs + ECs. Addition of anti-DMP blocks SMC- as well as homocysteine-mediated contraction. However, CIMP inhibits only homocysteine-mediated contraction. The results suggest that homocysteine may enhance vascular constrictive remodeling by inactivating PPAR-α and -γ in ECs and PPAR-γ in SMCs.

scholarly journals Clinical Evidence of Antidepressant Effects of Insulin and Anti-Hyperglycemic Agents and Implications for the Pathophysiology of Depression—A Literature Review

2020 ◽  
Vol 21 (18) ◽  
pp. 6969
Author(s):  
Young Sup Woo ◽  
Hyun Kook Lim ◽  
Sheng-Min Wang ◽  
Won-Myong Bahk
Keyword(s):  
Insulin Resistance ◽  
Clinical Trials ◽  
Molecular Mechanisms ◽  
Experimental Studies ◽  
Antidepressant Effect ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Glucagon Like Peptide 1 ◽  
Review Reports

Close connections between depression and type 2 diabetes (T2DM) have been suggested by many epidemiological and experimental studies. Disturbances in insulin sensitivity due to the disruption of various molecular pathways cause insulin resistance, which underpins many metabolic disorders, including diabetes, as well as depression. Several anti-hyperglycemic agents have demonstrated antidepressant properties in clinical trials, probably due to their action on brain targets based on the shared pathophysiology of depression and T2DM. In this article, we review reports of clinical trials examining the antidepressant effect of these medications, including insulin, metformin, glucagon like peptide-1 receptor agonists (GLP-1RA), and peroxisome proliferator-activated receptor (PPAR)-γ agonists, and briefly consider possible molecular mechanisms underlying the associations between amelioration of insulin resistance and improvement of depressive symptoms. In doing so, we intend to suggest an integrative perspective for understanding the pathophysiology of depression.

scholarly journals Peroxisome Proliferator-Activated Receptor Agonists: Do They Increase Cardiovascular Risk?

PPAR Research ◽  
2009 ◽  
Vol 2009 ◽  
pp. 1-7 ◽  
Author(s):  
Ahmad Aljada ◽  
Kshitij Ashwin Shah ◽  
Shaker A. Mousa
Keyword(s):  
Molecular Mechanisms ◽  
Review Article ◽  
Current Evidence ◽  
Peroxisome Proliferator ◽  
Cardiovascular Risks ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Agonists ◽  
Record Trial ◽  
Meta Analyses

Cardiovascular disease is a major cause of morbidity and mortality among people with type 2 diabetes mellitus. The peroxisome proliferator-activated receptor (PPAR) agonists have a significant role on glucose and fat metabolism. Thiazolidinediones (TZDs) are predominantly PPARγagonists, and their primary benefit appears to be the prevention of diabetic complications by improving glycemic control and lipid profile. Recently, the cardiovascular safety of rosiglitazone was brought to center stage following meta analyses and the interim analysis of the RECORD trial. Current evidence points to rosiglitazone having a greater risk of myocardial ischemic events than placebo, metformin, or sulfonylureas. This review article discusses the mechanism of action of PPAR agonists and correlates it with clinical and laboratory outcomes in the published literature. In addition, this review article attempts to discuss some of the molecular mechanisms regarding the association between TZDs therapy and the nontraditional cardiovascular risks.

scholarly journals Activation of peroxisome proliferator-activated receptor-γ by rosiglitazone improves lipid homeostasis at the adipose tissue-liver axis in ethanol-fed mice

2012 ◽  
Vol 302 (5) ◽  
pp. G548-G557 ◽  
Author(s):  
Xiuhua Sun ◽  
Yunan Tang ◽  
Xiaobing Tan ◽  
Qiong Li ◽  
Wei Zhong ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Fatty Liver ◽  
Ethanol Exposure ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Acid Uptake ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Peroxisomal Fatty Acid

The development of alcohol-induced fatty liver is associated with a reduction of white adipose tissue (WAT). Peroxisome proliferator-activated receptor (PPAR)-γ prominently distributes in the WAT and plays a crucial role in maintaining adiposity. The present study investigated the effects of PPAR-γ activation by rosiglitazone on lipid homeostasis at the adipose tissue-liver axis. Adult C57BL/6 male mice were pair fed liquid diet containing ethanol or isocaloric maltose dextrin for 8 wk with or without rosiglitazone supplementation to ethanol-fed mice for the last 3 wk. Ethanol exposure downregulated adipose PPAR-γ gene and reduced the WAT mass in association with induction of inflammation, which was attenuated by rosiglitazone. Ethanol exposure stimulated lipolysis but reduced fatty acid uptake capacity in association with dysregulation of lipid metabolism genes. Rosiglitazone normalized adipose gene expression and corrected ethanol-induced lipid dyshomeostasis. Ethanol exposure induced steatosis and upregulated inflammatory genes in the liver, which were attenuated by rosiglitazone. Hepatic peroxisomal fatty acid β-oxidation was suppressed by ethanol in associated with inhibition of acyl-coenzyme A oxidase 1. Rosiglitazone elevated plasma adiponectin level and normalized peroxisomal fatty acid β-oxidation rate. However, rosiglitazone did not affect ethanol-reduced very low-density lipoprotein secretion from the liver. These results demonstrated that activation of PPAR-γ by rosiglitazone reverses ethanol-induced adipose dysfunction and lipid dyshomeostasis at the WAT-liver axis, thereby abrogating alcoholic fatty liver.

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