scholarly journals PPARγNetworks in Cell Signaling: Update and Impact of Cyclic Phosphatidic Acid

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Tamotsu Tsukahara
Keyword(s):  
Phosphatidic Acid ◽  
Biologically Active ◽  
Peroxisome Proliferator ◽  
Glycerol Phosphate ◽  
Peroxisome Proliferator Activated Receptor ◽  
Pharmacological Interest ◽  
Sphingosine 1 Phosphate ◽  
Cyclic Phosphatidic Acid ◽  
G Protein Coupled ◽  
Therapeutic Compound

Lysophospholipid (LPL) has long been recognized as a membrane phospholipid metabolite. Recently, however, the LPL has emerged as a candidate for diagnostic and pharmacological interest. LPLs include lysophosphatidic acid (LPA), alkyl glycerol phosphate (AGP), cyclic phosphatidic acid (cPA), and sphingosine-1-phosphate (S1P). These biologically active lipid mediators serve to promote a variety of responses that include cell proliferation, migration, and survival. These LPL-related responses are mediated by cell surface G-protein-coupled receptors and also intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). In this paper, we focus mainly on the most recent findings regarding the biological function of nuclear receptor-mediated lysophospholipid signaling in mammalian systems, specifically as they relate to health and diseases. Also, we will briefly review the biology of PPARγand then provide an update of lysophospholipids PPARγligands that are under investigation as a therapeutic compound and which are targets of PPARγrelevant to diseases.

scholarly journals Hyperthyroidism Evokes Myocardial Ceramide Accumulation

2015 ◽  
Vol 35 (2) ◽  
pp. 755-766 ◽  
Author(s):  
Agnieszka Mikłosz ◽  
Bartłomiej Łukaszuk ◽  
Adrian Chabowski ◽  
Filip Rogowski ◽  
Krzysztof Kurek ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Cardiac Physiology ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sphingosine 1 Phosphate ◽  
Male Wistar Rats ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Cpt I ◽  
Amp Activated Protein Kinase ◽  
Ceramide Accumulation

Background: Thyroid hormones (THs) are key regulators of cardiac physiology as well as modulators of different cellular signals including the sphingomyelin/ceramide pathway. The objective of this study was to examine the effect of hyperthyroidism on the metabolism of sphingolipids in the muscle heart. Methods: Male Wistar rats were treated for 10 days with triiodothyronine (T3) at a dose of 50µg/100g of body weight. Animals were then anaesthetized and samples of the left ventricle were excised. Results: We have demonstrated that prolonged, in vivo, T3 treatment increased the content of sphinganine (SFA), sphingosine (SFO), ceramide (CER) and sphingomyelin (SM), but decreased the level of sphingosine-1-phosphate (S1P) in cardiac muscle. Accordingly, the changes in sphingolipids content were accompanied by a lesser activity of neutral sphingomyelinase and without significant changes in ceramidases activity. Hyperthyroidism also induced activation of AMP-activated protein kinase (AMPK) with subsequently increased expression of mitochondrial proteins: cytochrome c oxidase IV (COX IV), β-hydroxyacyl-CoA dehydrogenase (β-HAD), carnityne palmitoyltransferase I (CPT I) and nuclear peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α). Conclusions: We conclude that prolonged T3 treatment increases sphingolipids metabolism which is reflected by higher concentration of SFA and CER in heart muscle. Furthermore, hyperthyroidism-induced increase in heart sphingomyelin (SM) concentration might be one of the mechanisms underlying maintenance of CER at relatively low level by its conversion to SM together with decreased S1P content.

scholarly journals The Role of PPARγin the Transcriptional Control by Agonists and Antagonists

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Tamotsu Tsukahara
Keyword(s):  
Transcriptional Repression ◽  
Transcriptional Control ◽  
Thyroid Hormone Receptor ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cyclic Phosphatidic Acid

In recent years, peroxisome proliferator-activated receptor gamma (PPARγ) has been reported to be a target for the treatment of type II diabetes. Furthermore, it has received attention for its therapeutic potential in many other human diseases, including atherosclerosis, obesity, and cancers. Recent studies have provided evidence that the endogenously produced PPARγ antagonist, 2,3-cyclic phosphatidic acid (cPA), which is similar in structure to lysophosphatidic acid (LPA), inhibits cancer cell invasion and metastasisin vitroandin vivo. We recently observed that cPA negatively regulates PPARγ function by stabilizing the binding of the corepressor protein, silencing mediator of retinoic acid and thyroid hormone receptor. We also showed that cPA prevents neointima formation, adipocyte differentiation, lipid accumulation, and upregulation of PPARγ target gene transcription. We then analyzed the molecular mechanism of cPA's action on PPARγ. In this paper, we summarize the current knowledge on the mechanism of PPARγ-mediated transcriptional activity and transcriptional repression in response to novel lipid-derived ligands, such as cPA.

Insulinotropic effects of GPR120 agonists are altered in obese diabetic and obese non-diabetic states

2017 ◽  
Vol 131 (3) ◽  
pp. 247-260 ◽  
Author(s):  
Dan Zhang ◽  
Wing Yan So ◽  
Yi Wang ◽  
Shang Ying Wu ◽  
Qianni Cheng ◽  
...  
Keyword(s):  
G Protein ◽  
Peroxisome Proliferator ◽  
G Protein Coupled Receptor ◽  
Β Cells ◽  
Peroxisome Proliferator Activated Receptor ◽  
G Protein Coupled

Resident G-protein-coupled receptor 120 (GPR120) activation exhibits insulinotropic effects in rodent islets and β-cells. GPR120 expression in β-cells and insulinotropic effects of GPR120 activation are changed in differential ways in obese non-diabetic (OND) and diabetic states. Peroxisome proliferator-activated receptor γ (PPARγ) may facilitate these alterations.

scholarly journals Peroxisome Proliferator-activated Receptor γ Regulates Expression of the Anti-lipolytic G-protein-coupled Receptor 81 (GPR81/Gpr81)

2009 ◽  
Vol 284 (39) ◽  
pp. 26385-26393 ◽  
Author(s):  
Ellen H. Jeninga ◽  
Anne Bugge ◽  
Ronni Nielsen ◽  
Sander Kersten ◽  
Nicole Hamers ◽  
...  
Keyword(s):  
G Protein ◽  
Peroxisome Proliferator ◽  
G Protein Coupled Receptor ◽  
Peroxisome Proliferator Activated Receptor ◽  
G Protein Coupled

Regulation of the metabolism of apolipoprotein M and sphingosine 1-phosphate by hepatic PPARγ activity

2018 ◽  
Vol 475 (12) ◽  
pp. 2009-2024 ◽  
Author(s):  
Makoto Kurano ◽  
Hitoshi Ikeda ◽  
Naoyuki Iso-O ◽  
Masumi Hara ◽  
Kazuhisa Tsukamoto ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
Mouse Liver ◽  
Kinase Activity ◽  
Sphingosine Kinase ◽  
Peroxisome Proliferator ◽  
Obese Mice ◽  
Peroxisome Proliferator Activated Receptor ◽  
Apolipoprotein M ◽  
Adenoviral Gene Transfer ◽  
Sphingosine 1 Phosphate

Apolipoprotein M (apoM) is a carrier and a modulator of sphingosine 1-phosphate (S1P), an important multifunctional bioactive lipid. Since peroxisome proliferator-activated receptor γ (PPARγ) is reportedly associated with the function and metabolism of S1P, we investigated the modulation of apoM/S1P homeostasis by PPARγ. First, we investigated the modulation of apoM and S1P homeostasis by the overexpression or knockdown of PPARγ in HepG2 cells and found that both the overexpression and the knockdown of PPARγ decreased apoM expression and S1P synthesis. When we activated or suppressed the PPARγ more mildly with pioglitazone or GW9662, we found that pioglitazone suppressed apoM expression and S1P synthesis, while GW9662 increased them. Next, we overexpressed PPARγ in mouse liver through adenoviral gene transfer and observed that both the plasma and hepatic apoM levels and the plasma S1P levels decreased, while the hepatic S1P levels increased, in the presence of enhanced sphingosine kinase activity. Treatment with pioglitazone decreased both the plasma and hepatic apoM and S1P levels only in diet-induced obese mice. Moreover, the overexpression of apoM increased, while the knockdown of apoM suppressed PPARγ activities in HepG2 cells. These results suggested that PPARγ regulates the S1P levels by modulating apoM in a bell-shaped manner, with the greatest levels of apoM/S1P observed when PPARγ was mildly expressed and that hepatic apoM/PPARγ axis might maintain the homeostasis of S1P metabolism.

scholarly journals Sphingosine 1-phosphate is a ligand for peroxisome proliferator-activated receptor-γ that regulates neoangiogenesis

2015 ◽  
Vol 29 (9) ◽  
pp. 3638-3653 ◽  
Author(s):  
Kate A. Parham ◽  
Julia R. Zebol ◽  
Katie L. Tooley ◽  
Wai Y. Sun ◽  
Lachlan M. Moldenhauer ◽  
...  
Keyword(s):  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Sphingosine 1 Phosphate

scholarly journals Bitter receptor TAS2R138 facilitates lipid droplet degradation in neutrophils during Pseudomonas aeruginosa infection

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Qinqin Pu ◽  
Kai Guo ◽  
Ping Lin ◽  
Zhihan Wang ◽  
Shugang Qin ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Taste Receptor ◽  
Local Environment ◽  
Homoserine Lactone ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Foreign Objects ◽  
Pseudomonas Aeruginosa Infection ◽  
Mouse Taste ◽  
G Protein Coupled

AbstractBitter receptors function primarily in sensing taste, but may also have other functions, such as detecting pathogenic organisms due to their agile response to foreign objects. The mouse taste receptor type-2 member 138 (TAS2R138) is a member of the G-protein-coupled bitter receptor family, which is not only found in the tongue and nasal cavity, but also widely distributed in other organs, such as the respiratory tract, gut, and lungs. Despite its diverse functions, the role of TAS2R138 in host defense against bacterial infection is largely unknown. Here, we show that TAS2R138 facilitates the degradation of lipid droplets (LDs) in neutrophils during Pseudomonas aeruginosa infection through competitive binding with PPARG (peroxisome proliferator-activated receptor gamma) antagonist: N-(3-oxododecanoyl)-l-homoserine lactone (AHL-12), which coincidently is a virulence-bound signal produced by this bacterium (P. aeruginosa). The released PPARG then migrates from nuclei to the cytoplasm to accelerate the degradation of LDs by binding PLIN2 (perilipin-2). Subsequently, the TAS2R138–AHL-12 complex targets LDs to augment their degradation, and thereby facilitating the clearance of AHL-12 in neutrophils to maintain homeostasis in the local environment. These findings reveal a crucial role for TAS2R138 in neutrophil-mediated host immunity against P. aeruginosa infection.

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