scholarly journals Recent Insights on the Role of PPAR-β/δ in Neuroinflammation and Neurodegeneration, and Its Potential Target for Therapy

2020 ◽  
Author(s):  
Anna K. Strosznajder ◽  
Sylwia Wójtowicz ◽  
Mieszko J. Jeżyna ◽  
Grace Y. Sun ◽  
Joanna B. Strosznajder
Keyword(s):  
Fatty Acids ◽  
Traumatic Injury ◽  
Brain Regions ◽  
Dietary Lipids ◽  
Peroxisome Proliferator ◽  
Special Role ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
The Impact ◽  
Long Chain

AbstractPeroxisome proliferator-activated receptor (PPAR) β/δ belongs to the family of hormone and lipid-activated nuclear receptors, which are involved in metabolism of long-chain fatty acids, cholesterol, and sphingolipids. Similar to PPAR-α and PPAR-γ, PPAR-β/δ also acts as a transcription factor activated by dietary lipids and endogenous ligands, such as long-chain saturated and polyunsaturated fatty acids, and selected lipid metabolic products, such as eicosanoids, leukotrienes, lipoxins, and hydroxyeicosatetraenoic acids. Together with other PPARs, PPAR-β/δ displays transcriptional activity through interaction with retinoid X receptor (RXR). In general, PPARs have been shown to regulate cell differentiation, proliferation, and development and significantly modulate glucose, lipid metabolism, mitochondrial function, and biogenesis. PPAR-β/δ appears to play a special role in inflammatory processes and due to its proangiogenic and anti-/pro-carcinogenic properties, this receptor has been considered as a therapeutic target for treating metabolic syndrome, dyslipidemia, carcinogenesis, and diabetes. Until now, most studies were carried out in the peripheral organs, and despite of its presence in brain cells and in different brain regions, its role in neurodegeneration and neuroinflammation remains poorly understood. This review is intended to describe recent insights on the impact of PPAR-β/δ and its novel agonists on neuroinflammation and neurodegenerative disorders, including Alzheimer’s and Parkinson’s, Huntington’s diseases, multiple sclerosis, stroke, and traumatic injury. An important goal is to obtain new insights to better understand the dietary and pharmacological regulations of PPAR-β/δ and to find promising therapeutic strategies that could mitigate these neurological disorders.

Immunomodulatory Role of PPAR-γ in Alveolar Macrophages

2008 ◽  
Vol 56 (2) ◽  
pp. 522-527 ◽  
Author(s):  
Raju C. Reddy
Keyword(s):  
Fatty Acids ◽  
Alveolar Macrophage ◽  
Alveolar Macrophages ◽  
Adaptive Immune System ◽  
Pulmonary Sarcoidosis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inhaled Particles ◽  
Ppar Γ ◽  
Inflammatory Stimuli

The lung is constantly exposed to inhaled pathogens and toxins yet totally dependent on the integrity of a delicate alveolar-capillary interface for its function. Much of the balance between protection and collateral damage rests on the alveolar macrophage, which not only phagocytoses inhaled particles but also modulates the activity of both innate and acquired immune systems to limit unnecessary or exuberant inflammation. In its resting state, the alveolar macrophage secretes anti-inflammatory mediators while limiting antigen presentation to the adaptive immune system. The alveolar macrophage's state of activation is regulated by a variety of factors, including the activity of the nuclear receptor peroxisome proliferator-activated receptor γ (PPAR-γ). Peroxisome proliferator-activated receptor γ agonists reduce the ability of inflammatory stimuli to activate the alveolar macrophage while simultaneously stimulating phagocytosis of both opsonized and unopsonized particles, via the Fcγ and CD36 receptors, respectively. All known endogenous PPAR-γ ligands are fatty acid derivatives, and macrophage-specific knockout of the enzyme that converts esterified fatty acids to free fatty acids results in severe lung inflammation. Peroxisome proliferator-activated receptor γ expression is reduced in alveolar macrophages from patients with pulmonary sarcoidosis and alveolar proteinosis, suggesting that the deficiency may play a role in pathogenesis of these diseases. In summary, these observations point to PPAR-γ in the context of the alveolar macrophage as a crucial factor in limiting excessive and possibly injurious inflammation in the lung.

scholarly journals Medium Chain Fatty Acids Are Selective Peroxisome Proliferator Activated Receptor (PPAR) γ Activators and Pan-PPAR Partial Agonists

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e36297 ◽  
Author(s):  
Marcelo Vizoná Liberato ◽  
Alessandro S. Nascimento ◽  
Steven D. Ayers ◽  
Jean Z. Lin ◽  
Aleksandra Cvoro ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Partial Agonists ◽  
Ppar Γ ◽  
Chain Fatty Acids

scholarly journals Dietary Lipids Influence Bioaccessibility of Polyphenols from Black Carrots and Affect Microbial Diversity under Simulated Gastrointestinal Digestion

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 762
Author(s):  
Chunhe Gu ◽  
Hafiz A. R. Suleria ◽  
Frank R. Dunshea ◽  
Kate Howell
Keyword(s):  
Fatty Acids ◽  
Gut Microbiome ◽  
Sunflower Oil ◽  
Coconut Oil ◽  
Dietary Lipids ◽  
Total Phenolic ◽  
Dietary Polyphenols ◽  
Reducing Ability ◽  
The Impact ◽  
Long Chain

The bioaccessibility and activity of polyphenols is dependent on their structure and entrapment in the food matrix. While dietary lipids are known to transit into the colon, the impact of different lipids on the microbiome, and their interactions with dietary polyphenols are largely unknown. Here, we investigated the effect of dietary lipids on the bioaccessibility of polyphenols from purple/black carrots and adaptation of the gut microbiome in a simulated in vitro digestion-fermentation. Coconut oil, sunflower oil, and beef tallow were selected to represent common dietary sources of medium-chain fatty acids (MCFAs), long-chain polyunsaturated fatty acids (PUFAs), and long-chain polysaturated fatty acids (SFAs), respectively. All lipids promoted the bioaccessibility of both anthocyanins and phenolic acids during intestinal digestion with coconut oil exhibiting the greatest protection of anthocyanins. Similar trends were shown in antioxidant assays (2,2-Diphenyl-1-pricrylhydrazyl (DPPH), ferric reducing ability (FRAP), and total phenolic content (TPC)) with higher phytochemical bioactivities observed with the addition of dietary lipids. Most bioactive polyphenols were decomposed during colonic fermentation. Black carrot modulated diversity and composition of a simulated gut microbiome. Dramatic shifts in gut microbiome were caused by coconut oil. Inclusion of sunflower oil improved the production of butyrate, potentially due to the presence of PUFAs. The results show that the impact of polyphenols in the digestive tract should be considered in the context of other components of the diet, particularly lipids.

Distinct transcriptional regulation of long-chain acyl-CoA synthetase isoforms and cytosolic thioesterase 1 in the rodent heart by fatty acids and insulin

2006 ◽  
Vol 290 (6) ◽  
pp. H2480-H2497 ◽  
Author(s):  
David J. Durgan ◽  
Justin K. Smith ◽  
Margaret A. Hotze ◽  
Oluwaseun Egbejimi ◽  
Karalyn D. Cuthbert ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acyl ◽  
Null Mouse ◽  
Peroxisome Proliferator ◽  
Futile Cycle ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Chain Acyl ◽  
Long Chain

The molecular mechanism(s) responsible for channeling long-chain fatty acids (LCFAs) into oxidative versus nonoxidative pathways is (are) poorly understood in the heart. Intracellular LCFAs are converted to long-chain fatty acyl-CoAs (LCFA-CoAs) by a family of long-chain acyl-CoA synthetases (ACSLs). Cytosolic thioesterase 1 (CTE1) hydrolyzes cytosolic LCFA-CoAs to LCFAs, generating a potential futile cycle at the expense of ATP utilization. We hypothesized that ACSL isoforms and CTE1 are differentially regulated in the heart during physiological and pathophysiological conditions. Using quantitative RT-PCR, we report that the five known acsl isoforms ( acsl1, acsl3, acsl4, acsl5, and acsl6) and cte1 are expressed in whole rat and mouse hearts, as well as adult rat cardiomyocytes (ARCs). Streptozotocin-induced insulin-dependent diabetes (4 wk) and fasting (≤24 h) both dramatically induced cte1 and repressed acsl6 mRNA, with no significant effects on the other acsl isoforms. In contrast, high-fat feeding (4 wk) induced cte1 without affecting expression of the acsl isoforms in the heart. Investigation into the mechanism(s) responsible for these transcriptional changes uncovered roles for peroxisome proliferator-activated receptor-α (PPARα) and insulin as regulators of specific acsl isoforms and cte1 in the heart. Culturing ARCs with oleate (0.1–0.4 mM) or the PPARα agonists WY-14643 (1 μM) and fenofibrate (10 μM) consistently induced acsl1 and cte1. Conversely, PPARα null mouse hearts exhibited decreased acsl1 and cte1 expression. Culturing ARCs with insulin (10 nM) induced acsl6, whereas specific loss of insulin signaling within the heart (cardiac-specific insulin receptor knockout mice) caused decreased acsl6 expression. Our data expose differential regulation of acsl isoforms and cte1 in the heart, where acsl1 and cte1 are PPARα-regulated genes, whereas acsl6 is an insulin-regulated gene.

scholarly journals Impacts of peroxisome proliferator-activated receptor-γ activation on cigarette smoke-induced exacerbated response to bacteria

2014 ◽  
Vol 45 (1) ◽  
pp. 191-200 ◽  
Author(s):  
Mathieu C. Morissette ◽  
Pamela Shen ◽  
Danya Thayaparan ◽  
Martin R. Stämpfli
Keyword(s):  
Cigarette Smoke ◽  
Treatment Options ◽  
Pulmonary Inflammation ◽  
Treatment Protocol ◽  
Bacterial Pathogen ◽  
Chronic Obstructive ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
The Impact

Chronic obstructive pulmonary disease (COPD) is characterised by a state of chronic pulmonary inflammation punctuated by microbial exacerbations. Despite advances in treatment options, COPD remains difficult to manage. In this study, we investigated the potential of peroxisome proliferator-activated receptor (PPAR)γ activation as a new therapy against cigarette smoke-induced inflammation and its associated bacterial exacerbation.C57BL/6 mice were exposed to room air or cigarette smoke for either 4 days or 4 weeks and treated either prophylactically or therapeutically with rosiglitazone. The impact of rosiglitazone on cigarette smoke-induced exacerbated response to the bacterial pathogen nontypeable Haemophilus influenzae (NTHi) was studied using the therapeutic treatment protocol.We found that rosiglitazone was able to reduce cigarette smoke-induced neutrophilia both when administered prophylactically or therapeutically. Therapeutic intervention with rosiglitazone was also effective in preventing cigarette smoke-induced neutrophilia exacerbation following NTHi infection. Moreover, the anti-inflammatory effects of rosiglitazone did not lead to an increase in the pulmonary bacterial burden, unlike dexamethasone.Altogether, our data suggest that pharmacological activation of PPARγ may be an effective therapeutic approach to improve COPD management, as it is able to reduce cigarette smoke-induced inflammation and decrease the magnitude of bacterial exacerbations, without compromising the ability of the immune system to control the infection.

scholarly journals Intestinal microbe-dependent ω3 lipid metabolite αKetoA prevents inflammatory diseases in mice and cynomolgus macaques

2022 ◽  
Author(s):  
Takahiro Nagatake ◽  
Shigenobu Kishino ◽  
Emiko Urano ◽  
Haruka Murakami ◽  
Nahoko Kitamura ◽  
...  
Keyword(s):  
Linolenic Acid ◽  
Octadecadienoic Acid ◽  
Inflammatory Diseases ◽  
Linseed Oil ◽  
Dietary Lipids ◽  
Contact Hypersensitivity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Cynomolgus Macaques

AbstractDietary ω3 fatty acids have important health benefits and exert their potent bioactivity through conversion to lipid mediators. Here, we demonstrate that microbiota play an essential role in the body’s use of dietary lipids for the control of inflammatory diseases. We found that amounts of 10-hydroxy-cis-12-cis-15-octadecadienoic acid (αHYA) and 10-oxo-cis-12-cis-15-octadecadienoic acid (αKetoA) increased in the feces and serum of specific-pathogen-free, but not germ-free, mice when they were maintained on a linseed oil diet, which is high in α-linolenic acid. Intake of αKetoA, but not αHYA, exerted anti-inflammatory properties through a peroxisome proliferator-activated receptor (PPAR)γ-dependent pathway and ameliorated hapten-induced contact hypersensitivity by inhibiting the development of inducible skin-associated lymphoid tissue through suppression of chemokine secretion from macrophages and inhibition of NF-κB activation in mice and cynomolgus macaques. Administering αKetoA also improved diabetic glucose intolerance by inhibiting adipose tissue inflammation and fibrosis through decreased macrophage infiltration in adipose tissues and altering macrophage M1/M2 polarization in mice fed a high-fat diet. These results collectively indicate that αKetoA is a novel postbiotic derived from α-linolenic acid, which controls macrophage-associated inflammatory diseases and may have potential for developing therapeutic drugs as well as probiotic food products.

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