scholarly journals PPAR-δin Vascular Pathophysiology

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Nanping Wang
Keyword(s):  
Transcription Factors ◽  
Cell Growth ◽  
Glucose Metabolism ◽  
Nuclear Receptor ◽  
Therapeutic Intervention ◽  
Peroxisome Proliferator ◽  
Cardiovascular Disorders ◽  
Direct Effects ◽  
Cell Growth And Differentiation ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors belong to the superfamily of ligand-dependent nuclear receptor transcription factors, which include three subtypes: PPAR-α,β/δ, andγ. PPAR-δ, play important roles in the regulation of cell growth and differentiation as well as tissue wound and repair. Emerging evidence has also demonstrated that PPAR-δis implicated in lipids and glucose metabolism. Most recently, the direct effects of PPAR-δon cardiovascular processes such as endothelial function and angiogenesis have also been investigated. Therefore, it is suggested that PPAR-δmay have critical roles in cardiovascular pathophysiology and is a potential target for therapeutic intervention of cardiovascular disorders such as atherosclerosis.

GLP-1-mediated delivery of the PPAR𝛼/𝛾 dual-agonist Tesaglitazar improves obesity and glucose metabolism in mice

2021 ◽  
Author(s):  
Carmelo Quarta ◽  
Kerstin Stemmer ◽  
Aaron Novikoff ◽  
Bin Yang ◽  
Felix Klingelhuber ◽  
...  
Keyword(s):  
Body Weight ◽  
Glucose Metabolism ◽  
Peroxisome Proliferator ◽  
Protein Targets ◽  
Beneficial Effects ◽  
Glucose And Lipid Metabolism ◽  
Therapeutic Value ◽  
Affect Body Weight ◽  
Peroxisome Proliferator Activated Receptors ◽  
Dual Agonist

Abstract Dual-agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPAR𝛼/𝛾) have shown beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to unfavorable cardiovascular and/or renal effects. Here we report the design and preclinical evaluation of a molecule that covalently links the PPAR𝛼/𝛾 dual-agonist Tesaglitazar to GLP-1 to allow for the GLP-1 receptor-dependent delivery of Tesaglitazar. GLP-1/Tesaglitazar does not differ from matched GLP-1 in GLP-1R signaling, but shows GLP-1R-dependent PPAR𝛾-RXR heterodimerization with enhanced efficacy to improve body weight, food intake, and glucose metabolism relative to GLP-1 or Tesaglitazar in mice with diet- and genetically-induced obesity. The conjugate fails to affect body weight and glucose metabolism in GLP-1R knockout (ko) mice and shows preserved effects in DIO mice at doses subthreshold for GLP-1 and Tesaglitazar to improve metabolism. Consistent with the GLP-1R expression pattern, LC/MS-based proteomics identified a series of novel PPAR protein targets in the hypothalamus that are acutely upregulated by Tesaglitazar and by GLP-1/Tesaglitazar, but not by treatment with GLP-1. Collectively, our data show that GLP-1/Tesaglitazar improves energy and glucose metabolism with superior efficacy to GLP-1 or Tesaglitazar alone and suggest that this conjugate holds therapeutic value to treat hyperglycemia and insulin resistance.

scholarly journals PPARs in Calorie Restricted and Genetically Long-Lived Mice

PPAR Research ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-7 ◽  
Author(s):  
Michal M. Masternak ◽  
Andrzej Bartke
Keyword(s):  
Transcription Factors ◽  
Energy Metabolism ◽  
Nuclear Receptors ◽  
Calorie Restriction ◽  
Insulin Action ◽  
Peroxisome Proliferator ◽  
Physiological Functions ◽  
Multiple Organs ◽  
Longevity Genes ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptors superfamily. The three subtypes, PPARα, PPARγ, and PPARβ/δ, are expressed in multiple organs. These transcription factors regulate different physiological functions such as energy metabolism (including lipid and carbohydrate metabolism), insulin action, and immunity and inflammation, and apparently also act as important mediators of longevity and aging. Calorie restriction (CR) is the most effective intervention known to delay aging and increase lifespan. Calorie restriction affects the same physiological functions as PPARs. This review summarizes recent findings on the effects of CR and aging on the expression of PPARγ,α, andβ/δin mice and discusses possible involvement of PPARs in mediating the effects of murine longevity genes. The levels of PPARs change with age and CR appears to prevent these alterations which make “PPARs-CR-AGING” dependence of considerable interest.

scholarly journals Peroxisome Proliferator-Activated Receptors and Shock State

2006 ◽  
Vol 6 ◽  
pp. 1770-1782 ◽  
Author(s):  
Emanuela Esposito ◽  
Salvatore Cuzzocrea ◽  
Rosaria Meli
Keyword(s):  
Transcription Factors ◽  
Energy Homeostasis ◽  
Hormone Receptors ◽  
Inflammatory Responses ◽  
Nuclear Hormone Receptor ◽  
Peroxisome Proliferator ◽  
Shock State ◽  
Anti Inflammatory ◽  
Peroxisome Proliferator Activated Receptors ◽  
Inflammatory Molecules

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors that are related to retinoid, steroid, and thyroid hormone receptors. Three isotypes of PPARs have been identified: alpha, beta/delta, and gamma, encoded by different genes and distributed in various tissues. PPARs are implicated in the control of inflammatory responses and in energy homeostasis and, thus, can be defined as metabolic and anti-inflammatory transcription factors. They exert anti-inflammatory effects by inhibiting the induction of proinflammatory cytokines, adhesion molecules, and extracellular matrix proteins, or by stimulating the production of anti-inflammatory molecules. Moreover, PPARs modulate the proliferation, differentiation, and survival of immune cells. This review presents the current state of knowledge regarding the involvement of PPARs in the control of inflammatory response, and their potential therapeutic applications in several types of shock, as well as hemorrhagic, septic, and nonseptic shock.

Peroxisome proliferator-activated receptor-γ as a novel and promising target for treating cancer via regulation of inflammation: A brief review

2021 ◽  
Vol 21 ◽  
Author(s):  
Yuvaraj S ◽  
B R Prashantha Kumar
Keyword(s):  
Transcription Factors ◽  
Cancer Cells ◽  
Animal Studies ◽  
Cell Metabolism ◽  
Ppar Gamma ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Physiological Processes ◽  
Promising Target ◽  
Peroxisome Proliferator Activated Receptors

: Peroxisome proliferator activated receptors (PPARs) are group of nuclear receptors and the ligand-activated intracellular transcription factors that are known to play a key role in physiological processes such as cell metabolism, proliferation, differentiation, tissue remodeling, inflammation, and atherosclerosis. However, in the past two decades, many reports claim that PPARs also play an imperious role as a tumor suppressor. PPAR- gamma (PPARγ), one of the best-known from the family of PPARs, is known to express in colon, breast, bladder, lung, and prostate cancer cells. Its function in tumour cells includes the modulation of several pathways involved in multiplication and apoptosis. The ligands of PPARγ act by PPARγ dependent as well as independent pathways and are also found to regulate different inflammatory mediators and transcription factors in systemic inflammation and in tumor microenvironment. Both synthetic and natural ligands that are known to activate PPARγ, suppress the tumor cell growth and multiplication through the regulation of inflammatory pathways, as found out from different functional assays and animal studies. Cancer and inflammation are interconnected process that are now being targeted to achieve tumor suppression by decreasing the risks and burden posed by cancer cells. Therefore, PPARγ can serve as a promising target for development of clinical drug molecule attenuating the proliferation of cancer cells. In this perspective, this mini review highlights the PPARγ as a potential target for drug development aiming for anti-inflammatory and thereby suppressing tumors.

scholarly journals A Retrospective on Nuclear Receptor Regulation of Inflammation: Lessons from GR and PPARs

PPAR Research ◽  
2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Min-Dian Li ◽  
Xiaoyong Yang
Keyword(s):  
Glucocorticoid Receptor ◽  
Signaling Pathways ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Receptor Regulation ◽  
Peroxisome Proliferator ◽  
Novel Therapies ◽  
Nuclear Receptor Superfamily ◽  
Founding Member ◽  
Peroxisome Proliferator Activated Receptors

Members of the nuclear receptor superfamily have vital roles in regulating immunity and inflammation. The founding member, glucocorticoid receptor (GR), is the prototype to demonstrate immunomodulation via transrepression of the AP-1 and NF-κB signaling pathways. Peroxisome proliferator-activated receptors (PPARs) have emerged as key regulators of inflammation. This review examines the history and current advances in nuclear receptor regulation of inflammation by the crosstalk with AP-1 and NF-κB signaling, focusing on the roles of GR and PPARs. A better understanding of the molecular mechanism by which nuclear receptors inhibit proinflammatory signaling pathways will enable novel therapies to treat chronic inflammation.

scholarly journals Peroxisome proliferator-activated receptors: a family of lipid-activated transcription factors

1999 ◽  
Vol 70 (4) ◽  
pp. 566-571 ◽  
Author(s):  
Steven D Clarke ◽  
Philippe Thuillier ◽  
Rebecca A Baillie ◽  
Xiaoming Sha
Keyword(s):  
Transcription Factors ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals Peroxisome Proliferator-Activated Receptors - Alpha in Chronic Inflammation - Mini-Review

2019 ◽  
Vol 12 ◽  
pp. 1-11
Author(s):  
Elena Popa ◽  
Florin Zugun-Eloae ◽  
Mihaela Zlei ◽  
Maria Traian ◽  
Agnes Bacusca ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Transcription Factors ◽  
Lipid Metabolism ◽  
Visceral Obesity ◽  
Peroxisome Proliferator ◽  
Proinflammatory Response ◽  
The Metabolic Syndrome ◽  
Metabolic Complication ◽  
Peroxisome Proliferator Activated Receptors ◽  
Proinflammatory Factors

The pathogeny of the metabolic syndrome (MetS ) is not fully elucidated, but a link between visceral obesity and the increase of the proinflammatory response was proven. Atherosclerosis, perceived as a metabolic complication, draws attention to the peroxisome proliferator-activated receptors- alpha (PPARα). PPARα receptors are transcription factors involved in lipid metabolism, inflammation and atheromatosis. Hence, it interferes in the pathogeny of cardiovascular diseases and other chronic diseases too (neurological, psychical, neoplasical). The study of the expression of PPARα and its modulation on different level may be beneficial in the treatment of metabolic syndrome, intervening in the modulation of another proinflammatory factors.

Sign in / Sign up

Export Citation Format

Share Document