Journal ArticleDOI
Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation.
TLDR
Findings indicate a modulatory role for PPARs in the control of the inflammatory response with potential therapeutic applications in inflammation-related diseases, such as atherosclerosis and inflammatory bowel disease.Abstract:
Peroxisome proliferator-activated (PPARs) are ligand-activated transcription factors belonging to the nuclear receptor family. PPARs function as regulators of lipid and lipoprotein metabolism and glucose homeostasis and influence cellular proliferation, differentiation and apoptosis. PPARalpha is highly expressed in tissues such as liver, muscle, kidney and heart, where it stimulates the beta-oxidative degradation of fatty acids. PPARgamma is predominantly expressed in intestine and adipose tissue. PPARgamma triggers adipocyte differentiation and promotes lipid storage. The hypolipidemic fibrates and the antidiabetic glitazones are synthetic ligands for PPARalpha and PPARgamma, respectively. Furthermore, fatty acids and eicosanoids are natural PPAR ligands: PPARalpha is activated by leukotriene B4, whereas prostaglandin J2 is a PPARgamma ligand. These observations suggested a potential role for PPARs not only in metabolic but also in inflammation control. The first evidence for a role of PPARalpha in inflammation control came from the demonstration that PPARalpha deficient mice display a prolonged response to inflammatory stimuli. It was suggested that PPARalpha deficiency results in a reduced beta-oxidative degradation of these inflammatory fatty acid derivatives. More recently, PPAR activators were shown to inhibit the activation of inflammatory response genes (such as IL-2, IL-6, IL-8, TNFalpha and metalloproteases) by negatively interfering with the NF- kappaB, STAT and AP-1 signalling pathways. PPAR activators exert these anti-inflammatory activities in different immunological and vascular wall cell types such as monocyte/macrophages, endothelial, epithelial and smooth muscle cells in which PPARs are expressed. These recent findings indicate a modulatory role for PPARs in the control of the inflammatory response with potential therapeutic applications in inflammation-related diseases, such as atherosclerosis and inflammatory bowel disease.read more
Citations
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Journal ArticleDOI
PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties.
M. Amine Bouhlel,M. Amine Bouhlel,M. Amine Bouhlel,Bruno Derudas,Bruno Derudas,Bruno Derudas,Elena Rigamonti,Elena Rigamonti,Elena Rigamonti,Rebecca Dièvart,Rebecca Dièvart,Rebecca Dièvart,John Brozek,Stéphan Haulon,Christophe Zawadzki,Brigitte Jude,Gérard Torpier,Gérard Torpier,Gérard Torpier,Nikolaus Marx,Bart Staels,Bart Staels,Bart Staels,Giulia Chinetti-Gbaguidi,Giulia Chinetti-Gbaguidi,Giulia Chinetti-Gbaguidi +25 more
TL;DR: It is shown that in human atherosclerotic lesions, the expression of M2 markers and PPARgamma, a nuclear receptor controlling macrophage inflammation, correlate positively, and that only native monocytes can be primed by PPARGamma activation to an enhanced M2 phenotype.
Journal ArticleDOI
Consumption of a Fat-Rich Diet Activates a Proinflammatory Response and Induces Insulin Resistance in the Hypothalamus
Cláudio T. De Souza,Eliana P. Araújo,Silvana Bordin,Rika Ashimine,Ricardo de Lima Zollner,Antonio Carlos Boschero,Mario J.A. Saad,Licio A. Velloso +7 more
TL;DR: It is concluded that HL feeding induces a local proinflammatory status in the hypothalamus, which results in impaired anorexigenic insulin signaling, which leads to a reduced caloric intake and weight loss.
Journal ArticleDOI
Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes
S. J. Creely,S. J. Creely,Philip G. McTernan,Christine M. Kusminski,Ff M. Fisher,N. F. da Silva,M. Khanolkar,Marc Evans,Alison L. Harte,Sudhesh Kumar,Sudhesh Kumar +10 more
TL;DR: T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response, and increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.
Journal ArticleDOI
The Nuclear Receptor Peroxisome Proliferator-Activated Receptor-α Mediates the Anti-Inflammatory Actions of Palmitoylethanolamide
Jesse Lo Verme,Jin Fu,Giuseppe Astarita,Giovanna La Rana,Roberto Russo,Antonio Calignano,Daniele Piomelli +6 more
TL;DR: Findings indicate that PPAR-α mediates the anti-inflammatory effects of PEA and suggest that this fatty-acid ethanolamide may serve, like its analog OEA, as an endogenous ligand of PPar-α.
Journal ArticleDOI
Polyunsaturated fatty acids and inflammation
TL;DR: The anti-inflammatory actions of long chain n-3 fatty acid-induced effects may be of therapeutic use in conditions with an acute or chronic inflammatory component.
References
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Journal ArticleDOI
An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ)
Jürgen M. Lehmann,Linda B. Moore,Tracey Smith-Oliver,William O. Wilkison,Timothy M. Willson,Steven A. Kliewer +5 more
TL;DR: It is reported that thiazolidinediones are potent and selective activators of peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily recently shown to function in adipogenesis, and raised the intriguing possibility that PPARγ is a target for the therapeutic actions of this class of compounds.
Journal ArticleDOI
The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation
Mercedes Ricote,Andrew C. Li,Andrew C. Li,Timothy M. Willson,Carolyn J. Kelly,Christopher K. Glass +5 more
TL;DR: It is shown that PPAR-γ is markedly upregulated in activated macrophages and inhibits the expression of the inducible nitric oxide synthase, gelatinase B and scavenger receptor A genes in response to 15d-PGJ2 and synthetic PPar-γ ligands, suggesting that PPARS and locally produced prostaglandin D2 metabolites are involved in the regulation of inflammatory responses.
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