scholarly journals The endocannabinoid pathway and the female reproductive organs

2012 ◽  
Vol 50 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Anna Maria Di Blasio ◽  
Michele Vignali ◽  
Davide Gentilini
Keyword(s):  
Signal Transduction ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Reproductive Organs ◽  
Signal Transduction Pathways ◽  
Peroxisome Proliferator ◽  
Pathological Conditions ◽  
Peroxisome Proliferator Activated Receptors ◽  
Synthesis And Degradation ◽  
Female Reproductive Organs

Endocannabinoids are endogenous ligands of cannabinoid, vanilloid and peroxisome proliferator-activated receptors that activate multiple signal transduction pathways. Together with their receptor and the enzymes responsible for their synthesis and degradation, these compounds constitute the endocannabinoid system that has been recently shown to play, in humans, an important role in modulating several central and peripheral functions including reproduction. Given the relevance of the system, drugs that are able to interfere with the activity of endocannabinoids are currently considered as candidates for the treatment of various diseases. In this review, we will summarise the current knowledge regarding the effects of endocannabinoids in female reproductive organs. In particular, we will focus on some newly reported mechanisms that can affect endometrial plasticity both in physiological and in pathological conditions.

scholarly journals Molecular Mechanisms of Obesity-Linked Cardiac Dysfunction: An Up-Date on Current Knowledge

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 629
Author(s):  
Jorge Gutiérrez-Cuevas ◽  
Ana Sandoval-Rodriguez ◽  
Alejandra Meza-Rios ◽  
Hugo Christian Monroy-Ramírez ◽  
Marina Galicia-Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cardiac Dysfunction ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Peroxisome Proliferator ◽  
White Adipocyte ◽  
Peroxisome Proliferator Activated Receptors ◽  
And Oxidative Stress

Obesity is defined as excessive body fat accumulation, and worldwide obesity has nearly tripled since 1975. Excess of free fatty acids (FFAs) and triglycerides in obese individuals promote ectopic lipid accumulation in the liver, skeletal muscle tissue, and heart, among others, inducing insulin resistance, hypertension, metabolic syndrome, type 2 diabetes (T2D), atherosclerosis, and cardiovascular disease (CVD). These diseases are promoted by visceral white adipocyte tissue (WAT) dysfunction through an increase in pro-inflammatory adipokines, oxidative stress, activation of the renin-angiotensin-aldosterone system (RAAS), and adverse changes in the gut microbiome. In the heart, obesity and T2D induce changes in substrate utilization, tissue metabolism, oxidative stress, and inflammation, leading to myocardial fibrosis and ultimately cardiac dysfunction. Peroxisome proliferator-activated receptors (PPARs) are involved in the regulation of carbohydrate and lipid metabolism, also improve insulin sensitivity, triglyceride levels, inflammation, and oxidative stress. The purpose of this review is to provide an update on the molecular mechanisms involved in obesity-linked CVD pathophysiology, considering pro-inflammatory cytokines, adipokines, and hormones, as well as the role of oxidative stress, inflammation, and PPARs. In addition, cell lines and animal models, biomarkers, gut microbiota dysbiosis, epigenetic modifications, and current therapeutic treatments in CVD associated with obesity are outlined in this paper.

scholarly journals Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

2021 ◽  
Vol 22 (2) ◽  
pp. 778
Author(s):  
Anna Stasiłowicz ◽  
Anna Tomala ◽  
Irma Podolak ◽  
Judyta Cielecka-Piontek
Keyword(s):  
Pharmacological Activity ◽  
Transient Receptor Potential ◽  
Cannabis Sativa ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Raw Material ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor

Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes. The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors. The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood–brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.

scholarly journals PPAR Action in Human Placental Development and Pregnancy and Its Complications

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-14 ◽  
Author(s):  
Fritz Wieser ◽  
Leslie Waite ◽  
Christophe Depoix ◽  
Robert N. Taylor
Keyword(s):  
Gestational Diabetes ◽  
Metabolic Regulation ◽  
Current Knowledge ◽  
Clinical Pregnancy ◽  
Trophoblast Invasion ◽  
Peroxisome Proliferator ◽  
Placental Development ◽  
Human Trophoblast ◽  
Peroxisome Proliferator Activated Receptors ◽  
Specific Disorders

During pregnancy crucial anatomic, physiologic, and metabolic changes challenge the mother and the fetus. The placenta is a remarkable organ that allows the mother and the fetus to adapt to the new metabolic, immunologic, and angiogenic environment imposed by gestation. One of the physiologic systems that appears to have evolved to sustain this metabolic regulation is mediated by peroxisome proliferator-activated receptors (PPARs). In clinical pregnancy-specific disorders, including preeclampsia, gestational diabetes, and intrauterine growth restriction, aberrant regulation of components of the PPAR system parallels dysregulation of metabolism, inflammation and angiogenesis. This review summarizes current knowledge on the role of PPARs in regulating human trophoblast invasion, early placental development, and also in the physiology of clinical pregnancy and its complications. As increasingly indicated in the literature, pregnancy disorders, such as preeclampsia and gestational diabetes, represent potential targets for treatment with PPAR ligands. With the advent of more specific PPAR agonists that exhibit efficacy in ameliorating metabolic, inflammatory, and angiogenic disturbances, further studies of their application in pregnancy-related diseases are warranted.

scholarly journals Inferring Aberrant Signal Transduction Pathways in Ovarian Cancer from TCGA Data

2014 ◽  
Vol 13s1 ◽  
pp. CIN.S13881 ◽  
Author(s):  
Richard Neapolitan ◽  
Xia Jiang
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Ovarian Carcinoma ◽  
Impact Analysis ◽  
Current Knowledge ◽  
The Cancer Genome Atlas ◽  
Gene Expression Level ◽  
Expression Level ◽  
Signal Transduction Pathways ◽  
Significance Level

This paper concerns a new method for identifying aberrant signal transduction pathways (STPs) in cancer using case/control gene expression-level datasets, and applying that method and an existing method to an ovarian carcinoma dataset. Both methods identify STPs that are plausibly linked to all cancers based on current knowledge. Thus, the paper is most appropriate for the cancer informatics community. Our hypothesis is that STPs that are altered in tumorous tissue can be identified by applying a new Bayesian network (BN)-based method (causal analysis of STP aberration (CASA)) and an existing method (signaling pathway impact analysis (SPIA)) to the cancer genome atlas (TCGA) gene expression-level datasets. To test this hypothesis, we analyzed 20 cancer-related STPs and 6 randomly chosen STPs using the 591 cases in the TCGA ovarian carcinoma dataset, and the 102 controls in all 5 TCGA cancer datasets. We identified all the genes related to each of the 26 pathways, and developed separate gene expression datasets for each pathway. The results of the two methods were highly correlated. Furthermore, many of the STPs that ranked highest according to both methods are plausibly linked to all cancers based on current knowledge. Finally, CASA ranked the cancer-related STPs over the randomly selected STPs at a significance level below 0.05 ( P = 0.047), but SPIA did not ( P = 0.083).

scholarly journals Peroxisome Proliferator-Activated Receptors and the Heart: Lessons from the Past and Future Directions

PPAR Research ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-18 ◽  
Author(s):  
Wang-Soo Lee ◽  
Jaetaek Kim
Keyword(s):  
Nuclear Family ◽  
Current Knowledge ◽  
Therapeutic Option ◽  
Lessons Learned ◽  
Peroxisome Proliferator ◽  
Main Role ◽  
Future Directions ◽  
Drug Candidates ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Peroxisome proliferator-activated receptors (PPARs) belong to the nuclear family of ligand activated transcriptional factors and comprise three different isoforms, PPAR-α, PPAR-β/δ, and PPAR-γ. The main role of PPARs is to regulate the expression of genes involved in lipid and glucose metabolism. Several studies have demonstrated that PPAR agonists improve dyslipidemia and glucose control in animals, supporting their potential as a promising therapeutic option to treat diabetes and dyslipidemia. However, substantial differences exist in the therapeutic or adverse effects of specific drug candidates, and clinical studies have yielded inconsistent data on their cardioprotective effects. This review summarizes the current knowledge regarding the molecular function of PPARs and the mechanisms of the PPAR regulation by posttranslational modification in the heart. We also describe the results and lessons learned from important clinical trials on PPAR agonists and discuss the potential future directions for this class of drugs.

scholarly journals The Role of Peroxisome Proliferator-Activated Receptors in the Development and Physiology of Gametes and Preimplantation Embryos

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-7 ◽  
Author(s):  
Jaou-Chen Huang
Keyword(s):  
Germ Cells ◽  
Current Knowledge ◽  
Polycystic Ovary ◽  
Preimplantation Embryos ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
X Receptors ◽  
Ppar Ligands

In several species, a family of nuclear receptors, the peroxisome proliferator-activated receptors (PPARs) composed of three isotypes, is expressed in somatic cells and germ cells of the ovary as well as the testis. Invalidation of these receptors in mice or stimulation of these receptors in vivo or in vitro showed that each receptor has physiological roles in the gamete maturation or the embryo development. In addition, synthetic PPARγligands are recently used to induce ovulation in women with polycystic ovary disease. These results reveal the positive actions of PPAR in reproduction. On the other hand, xenobiotics molecules (in herbicides, plasticizers, or components of personal care products), capable of activating PPAR, may disrupt normal PPAR functions in the ovary or the testis and have consequences on the quality of the gametes and the embryos. Despite the recent data obtained on the biological actions of PPARs in reproduction, relatively little is known about PPARs in gametes and embryos. This review summarizes the current knowledge on the expression and the function of PPARs as well as their partners, retinoid X receptors (RXRs), in germ cells and preimplantation embryos. The effects of natural and synthetic PPAR ligands will also be discussed from the perspectives of reproductive toxicology and assisted reproductive technology.

scholarly journals Endocannabinoids and endocannabinoid-like molecules are present in foods, blood and ileal fluids from ileostomy subjects: insight into possible metabolic implications

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Silvia Tagliamonte ◽  
Chris I R. Gill ◽  
Laura Kirsty Pourshahidi ◽  
Mary Slevin ◽  
Roger Lawther ◽  
...  
Keyword(s):  
Nervous System ◽  
Intestinal Tract ◽  
Cannabinoid Receptors ◽  
Endocannabinoid System ◽  
The Body ◽  
Intestinal Lumen ◽  
Healthy Population ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors ◽  
Gastro Intestinal Tract

AbstractThe endocannabinoid system is a lipid signalling system with several regulatory functions throughout the body including regulation of appetite, food intake, macronutrient metabolism, pain sensation, blood pressure, mood, cognition and immunity. It consists of endocannabinoids (ECs), their receptors and enzymes involved in their synthesis and degradation. The two best-characterized endocannabinoids are N-arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG). They are ligands of cannabinoid receptors CB1 and CB2 which are located in the central nervous system (CNS) but also in in the enteric nervous system, in the liver and in the adipose tissue.Several structural congeners of ECs including N-acylethanolamines (NAEs) such as oleoylethanolamine (OEA), linoleyethanolamine (LEA), and palmitoyletahanolamine (PEA), show similar mechanisms of action, tissue distribution as well as pathways of formation and breakdown. They are considered “endocannabinoid-like” molecules acting through receptors that are located both in CNS and in the gastro-intestinal tract mucosa such as the G-protein coupled receptor 119 (GPR119) and peroxisome proliferator-activated receptors (PPARs). NAEs display EC50 values for human GPR119 and PPAR-α between 65 ng/mL and 1000 ng/mL. Some evidence indicated that NAEs, their phosphorylated precursors N-acylphosphatidylethanolamines (NAPEs) and ECs are also present in food. Thus, we developed a food database of these molecules and we calculated the daily dietary intake in a healthy population.This study aimed to evaluate whether the concentrations of NAPEs, NAEs and ECs in the human intestinal lumen may support their activity through the receptors lining in the gastro-intestinal tract and if they correlated with those in plasma.The observational study (16/NI/0267, Ulster University) involved 35 ileostomists (18F/17M, aged 18–70 y, BMI 17–40 kg/m2) who collected overnight fasting samples of ileal fluid and plasma. The concentrations of NAEs, NAPEs and ECs in biological samples were determined by LC-HRMS.Data showed that NAEs and NAPEs were present in ileal fluids and plasma from all subjects ranging between 46851.0–104742.8 ng/mL and 0.3–59.6 ng/mL in ileal samples and 1159.4–3985.7 ng/mL and 0.19–1.24 ng/mL in plasma, respectively. Contrarily, no ECs in ileal fluids were found except 2-AG in two ileal samples whereas they ranged between 1.6–22.3 ng/mL in plasma. Differences between genders and associations of plasma levels with individual energy intakes were found.Altogether, the data demonstrated that NAEs in the intestinal lumen are sufficient to elicit metabolic responses through the gastro-intestinal receptors.

scholarly journals Beyond the Canonical Endocannabinoid System. A Screening of PPAR Ligands as FAAH Inhibitors

2020 ◽  
Vol 21 (19) ◽  
pp. 7026
Author(s):  
Leonardo Brunetti ◽  
Antonio Carrieri ◽  
Luca Piemontese ◽  
Paolo Tortorella ◽  
Fulvio Loiodice ◽  
...  
Keyword(s):  
Endocannabinoid System ◽  
Docking Study ◽  
Binding Mode ◽  
Peroxisome Proliferator ◽  
System A ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Ppar Ligands ◽  
Faah Inhibitors ◽  
Further Development

In recent years, Peroxisome Proliferator-Activated Receptors (PPARs) have been connected to the endocannabinoid system. These nuclear receptors indeed mediate the effects of anandamide and similar substances such as oleoyl-ethanolamide and palmitoyl-ethanolamide. An increasing body of literature describing the interactions between the endocannabinoid system and PPARs has slowly but surely been accumulating over the past decade, and a multitarget approach involving these receptors and endocannabinoid degrading enzyme FAAH has been proposed for the treatment of inflammatory states, cancer, and Alzheimer’s disease. The lack of knowledge about compounds endowed with such an activity profile therefore led us to investigate a library of readily available, well-characterized PPAR agonists that we had synthesized over the years in order to find a plausible lead compound for further development. Moreover, we propose a rationalization of our results via a docking study, which sheds some light on the binding mode of these PPAR agonists to FAAH and opens the way for further research in this field.

scholarly journals PPARs and Female Reproduction: Evidence from Genetically Manipulated Mice

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-8 ◽  
Author(s):  
Jichun Yang ◽  
Lihong Chen ◽  
Xiaoyan Zhang ◽  
Yunfeng Zhou ◽  
Dongjuan Zhang ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Gene Knockout ◽  
Critical Role ◽  
Large Body ◽  
Reproductive Organs ◽  
Transgenic Animal ◽  
Peroxisome Proliferator ◽  
Female Reproduction ◽  
Peroxisome Proliferator Activated Receptors ◽  
Genetically Manipulated

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors controlling many important physiological processes, including lipid and glucose metabolism, energy homeostasis, inflammation, as well as cell proliferation and differentiation. In the past decade, intensive study of PPARs has shed novel insight into prevention and treatment of dyslipidemia, insulin resistance, and type 2 diabetes. Recently, a large body of research revealed that PPARs are also functionally expressed in reproductive organs and various parts of placenta during pregnancy, which strongly suggests that PPARs might play a critical role in reproduction and development, in addition to their central actions in energy homeostasis. In this review, we summarize recent findings elucidating the role of PPARs in female reproduction, with particular focus on evidence from gene knockout and transgenic animal model study.

Sign in / Sign up

Export Citation Format

Share Document