Peroxisome proliferator-activated receptor gamma expression along the male genital system and its role in male fertility

2020 ◽  
Vol 35 (9) ◽  
pp. 2072-2085
Author(s):  
Marta Santoro ◽  
Francesca De Amicis ◽  
Saveria Aquila ◽  
Daniela Bonofiglio
Keyword(s):  
Male Fertility ◽  
Energy Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Close Link ◽  
Fatty Acid Derivatives ◽  
Reproductive Axis ◽  
Cell Proliferation And Differentiation ◽  
Pparγ Expression

ABSTRACT Peroxisome proliferator-activated receptor gamma (PPARγ) acts as a ligand activated transcription factor and regulates processes, such as energy homeostasis, cell proliferation and differentiation. PPARγ binds to DNA as a heterodimer with retinoid X receptor and it is activated by polyunsaturated fatty acids and fatty acid derivatives, such as prostaglandins. In addition, the insulin-sensitizing thiazolidinediones, such as rosiglitazone, are potent and specific activators of PPARγ. PPARγ is present along the hypothalamic–pituitary–testis axis and in the testis, where low levels in Leydig cells and higher levels in Sertoli cells as well as in germ cells have been found. High amounts of PPARγ were reported in the normal epididymis and in the prostate, but the receptor was almost undetectable in the seminal vesicles. Interestingly, in the human and in pig, PPARγ protein is highly expressed in ejaculated spermatozoa, suggesting a possible role of PPARγ signaling in the regulation of sperm biology. This implies that both natural and synthetic PPARγ ligands may act directly on sperm improving its performance. Given the close link between energy balance and reproduction, activation of PPARγ may have promising metabolic implications in male reproductive functions. In this review, we first describe PPARγ expression in different compartments of the male reproductive axis. Subsequently, we discuss the role of PPARγ in both physiological and several pathological conditions related to the male fertility.

scholarly journals Peroxisome Proliferator-Activated Receptor γ and PGC-1α in Cancer: Dual Actions as Tumor Promoter and Suppressor

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Seong-Hoon Yun ◽  
Sang-Heum Han ◽  
Joo-In Park
Keyword(s):  
Metabolic Pathways ◽  
Energy Homeostasis ◽  
Tumor Promoter ◽  
Clinical Implications ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Interacting Protein ◽  
Action Mechanisms ◽  
Important Regulator

Peroxisome proliferator-activated receptor γ (PPARγ) is part of a nuclear receptor superfamily that regulates gene expression involved in cell differentiation, proliferation, immune/inflammation response, and lipid metabolism. PPARγ coactivator-1α (PGC-1α), initially identified as a PPARγ-interacting protein, is an important regulator of diverse metabolic pathways, such as oxidative metabolism and energy homeostasis. The role of PGC-1α in diabetes, neurodegeneration, and cardiovascular disease is particularly well known. PGC-1α is also now known to play important roles in cancer, independent of the role of PPARγ in cancer. Though many researchers have studied the expression and clinical implications of PPARγ and PGC-1α in cancer, there are still many controversies about the role of PPARγ and PGC-1α in cancer. This review examines and summarizes some recent data on the role and action mechanisms of PPARγ and PGC-1α in cancer, respectively, particularly the recent progress in understanding the role of PPARγ in several cancers since our review was published in 2012.

scholarly journals PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice

2020 ◽  
Vol 21 (6) ◽  
pp. 2061 ◽  
Author(s):  
Yaping Wang ◽  
Takero Nakajima ◽  
Frank J. Gonzalez ◽  
Naoki Tanaka
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Cancer ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolic Regulators

Peroxisome proliferator-activated receptor (PPAR) α, β/δ, and γ modulate lipid homeostasis. PPARα regulates lipid metabolism in the liver, the organ that largely controls whole-body nutrient/energy homeostasis, and its abnormalities may lead to hepatic steatosis, steatohepatitis, steatofibrosis, and liver cancer. PPARβ/δ promotes fatty acid β-oxidation largely in extrahepatic organs, and PPARγ stores triacylglycerol in adipocytes. Investigations using liver-specific PPAR-disrupted mice have revealed major but distinct contributions of the three PPARs in the liver. This review summarizes the findings of liver-specific PPAR-null mice and discusses the role of PPARs in the liver.

scholarly journals Peroxisome Proliferator-Activated Receptor-Gamma Reduces ER Stress and Inflammation via Targeting NGBR Expression

2022 ◽  
Vol 12 ◽  
Author(s):  
Jialing Ma ◽  
Peng Zeng ◽  
Lipei Liu ◽  
Mengmeng Zhu ◽  
Juan Zheng ◽  
...  
Keyword(s):  
Er Stress ◽  
Promoter Region ◽  
Essential Role ◽  
Inhibitory Effect ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Cells ◽  
Pparγ Expression

Increased Nogo-B receptor (NGBR) expression in the liver improves insulin sensitivity by reducing endoplasmic reticulum stress (ER stress) and activating the AMPK pathway, although it remains elusive the mechanisms by which NGBR is induced. In this study, we found that PPARγ ligands (rosiglitazone or pioglitazone) increased NGBR expression in hepatic cells and HUVECs. Furthermore, promoter analysis defined two PPREs (PPARγ-responsive elements) in the promoter region of NGBR, which was further confirmed by the ChIP assay. In vivo, using liver-specific PPARγ deficient (PPARγLKO) mice, we identified the key role of PPARγ expression in pioglitazone-induced NGBR expression. Meanwhile, the basal level of ER stress and inflammation was slightly increased by NGBR knockdown. However, the inhibitory effect of rosiglitazone on inflammation was abolished while rosiglitazone-inhibited ER stress was weakened by NGBR knockdown. Taken together, these findings show that NGBR is a previously unrecognized target of PPARγ activation and plays an essential role in PPARγ-reduced ER stress and inflammation.

scholarly journals Peroxisome Proliferator-Activated Receptor Alpha Target Genes

PPAR Research ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-20 ◽  
Author(s):  
Maryam Rakhshandehroo ◽  
Bianca Knoch ◽  
Michael Müller ◽  
Sander Kersten
Keyword(s):  
Energy Homeostasis ◽  
Target Genes ◽  
Biological Function ◽  
Molecular Target ◽  
Peroxisome Proliferator ◽  
Biological Processes ◽  
Nutrient Metabolism ◽  
Peroxisome Proliferator Activated Receptor ◽  
Receptor Alpha

The peroxisome proliferator-activated receptor alpha (PPARα) is a ligand-activated transcription factor involved in the regulation of a variety of processes, ranging from inflammation and immunity to nutrient metabolism and energy homeostasis. PPARαserves as a molecular target for hypolipidemic fibrates drugs which bind the receptor with high affinity. Furthermore, PPARαbinds and is activated by numerous fatty acids and fatty acid-derived compounds. PPARαgoverns biological processes by altering the expression of a large number of target genes. Accordingly, the specific role of PPARαis directly related to the biological function of its target genes. Here, we present an overview of the involvement of PPARαin lipid metabolism and other pathways through a detailed analysis of the different known or putative PPARαtarget genes. The emphasis is on gene regulation by PPARαin liver although many of the results likely apply to other organs and tissues as well.

scholarly journals Macrophage CGI-58 Attenuates Inflammatory Responsiveness via Promotion of PPARγ Signaling

2016 ◽  
Vol 38 (2) ◽  
pp. 696-713 ◽  
Author(s):  
Dan Yang ◽  
Haimei Chen ◽  
Xu Zeng ◽  
Ping Xie ◽  
Xincun Wang ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Serum Levels ◽  
Histone Deacetylation ◽  
Raw264.7 Cells ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Signaling ◽  
Pparγ Expression

Background/Aims: Comparative gene identification-58 (CGI-58), an adipose triglyceride lipase (ATGL) coactivator, strongly promotes ATGL-mediated triglyceride (TG) catabolism. Beyond its function in promoting lipolysis, other features of CGI-58 have been proposed. Here, we investigated the role of CGI-58 in the regulation of inflammatory responsiveness in macrophages. Methods: Macrophage-specific GCI-58 transgenic mice (TG) and wild type mice (WT) were fed a high fat diet (HFD), and RAW264.7 cells were treated with lipopolysaccharide (LPS). The peroxisome proliferator-activated receptor (PPAR) signaling was detected. The inflammatory responsiveness and mitochondrial function were examined. Results: TG mice showed lower serum levels of proinflammatory cytokines and better mitochondrial function in macrophages compared with WT control. Knockdown of CGI-58 in RAW264.7 cells aggravated LPS-induced inflammation and mitochondrial dysfunction. CGI-58 overexpression and silencing in macrophages induced and inhibited PPARγ expression and activity, respectively. Most importantly, the PPARγ-specific agonist rosiglitazone significantly suppressed inflammation and mitochondrial dysfunction induced by CGI-58 deficiency. Furthermore, knockdown of PPARγ in macrophages significantly dampened the role of CGI-58 in suppression of inflammation and mitochondrial dysfunction. Interestingly, CGI-58 inhibited histone deacetylation and the recruitment of histone deacetylase (HDAC) to the PPARγ promoter. Finally, ATGL deficiency did not affect inflammatory responsiveness and PPARγ signaling in macrophages. Conclusion: These results demonstrate that macrophage CGI-58 enhances PPARγ signaling and thus suppresses inflammatory responsiveness and mitochondrial dysfunction.

scholarly journals Investigating the Role of PPARβ/δ in Retinal Vascular Remodeling Using Pparβ/δ-Deficient Mice

2020 ◽  
Vol 21 (12) ◽  
pp. 4403 ◽  
Author(s):  
Sze Yuan Ho ◽  
Yuet Ping Kwan ◽  
Beiying Qiu ◽  
Alison Tan ◽  
Hannah Louise Murray ◽  
...  
Keyword(s):  
Blood Vessel ◽  
Energy Homeostasis ◽  
Critical Role ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Blood Vessel Formation ◽  
Vessel Formation ◽  
Vessel Remodeling ◽  
Deficient Mice

Peroxisome proliferator-activated receptor (PPAR)β/δ is a member of the nuclear receptor superfamily of transcription factors, which plays fundamental roles in cell proliferation and differentiation, inflammation, adipogenesis, and energy homeostasis. Previous studies demonstrated a reduced choroidal neovascularization (CNV) in Pparβ/δ-deficient mice. However, PPARβ/δ’s role in physiological blood vessel formation and vessel remodeling in the retina has yet to be established. Our study showed that PPARβ/δ is specifically required for disordered blood vessel formation in the retina. We further demonstrated an increased arteriovenous crossover and wider venous caliber in Pparβ/δ-haplodeficient mice. In summary, these results indicated a critical role of PPARβ/δ in pathological angiogenesis and blood vessel remodeling in the retina.

Molecular control of circadian metabolic rhythms

2009 ◽  
Vol 107 (6) ◽  
pp. 1959-1964 ◽  
Author(s):  
Siming Li ◽  
Jiandie D. Lin
Keyword(s):  
Regulatory Networks ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Temporal Organization ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Control ◽  
Lipid Disorders

Circadian metabolic rhythms are fundamental to the control of nutrient and energy homeostasis, as well as the pathogenesis of metabolic disease, such as obesity, lipid disorders, and type 2 diabetes. This temporal organization of tissue metabolism is coordinated through reciprocal cross talk between the biological timing system and the metabolic regulatory networks. In this review, we discuss the signaling mechanisms that serve to couple metabolic regulation to the circadian pacemaker, in particular the role of the peroxisome proliferator-activated receptor-γ coactivator-1 transcriptional coactivators in integrating clock and energy metabolism.

Constitutive activation of p46JNK2 is indispensable for C/EBPδ induction in the initial stage of adipogenic differentiation

2017 ◽  
Vol 474 (20) ◽  
pp. 3421-3437 ◽  
Author(s):  
Joji Kusuyama ◽  
Tomokazu Ohnishi ◽  
Kenjiro Bandow ◽  
Muhammad Subhan Amir ◽  
Kaori Shima ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Energy Homeostasis ◽  
Early Stage ◽  
Adipogenic Differentiation ◽  
Endocrine System ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Initial Stage

Adipogenic differentiation plays a vital role in energy homeostasis and endocrine system. Several transcription factors, including peroxisome proliferator-activated receptor gamma 2 and CCAAT–enhancer-binding protein (C/EBP) α, β, and δ, are important for the process, whereas the stage-specific intracellular signal transduction regulating the onset of adipogenesis remains enigmatic. Here, we explored the functional role of c-jun N-terminal kinases (JNKs) in adipogenic differentiation using in vitro differentiation models of 3T3-L1 cells and primary adipo-progenitor cells. JNK inactivation with either a pharmacological inhibitor or JNK2-specific siRNA suppressed adipogenic differentiation, characterized by decreased lipid droplet appearance and the down-regulation of Adiponectin, fatty acid protein 4 (Fabp4), Pparg2, and C/ebpa expressions. Conversely, increased adipogenesis was observed by the inducible overexpression of p46JNK2 (JNK2-1), whereas it was not observed by that of p54JNK2 (JNK2-2), indicating a distinct role of p46JNK2. The essential role of JNK appears restricted to the early stage of adipogenic differentiation, as JNK inhibition in the later stages did not influence adipogenesis. Indeed, JNK phosphorylation was significantly induced at the onset of adipogenic differentiation. As for the transcription factors involved in early adipogenesis, JNK inactivation significantly inhibited the induction of C/ebpd, but not C/ebpb, during the initial stage of adipogenic differentiation. JNK activation increased C/ebpd mRNA and protein expression through the induction and phosphorylation of activating transcription factor 2 (ATF2) that binds to a responsive element within the C/ebpd gene promoter region. Taken together, these data indicate that constitutive JNK activity is specifically required for the initial stage differentiation events of adipocytes.

scholarly journals Regulation of Cell Proliferation and Differentiation by PPARβ/δ

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-5 ◽  
Author(s):  
Rolf Müller ◽  
Markus Rieck ◽  
Sabine Müller-Brüsselbach
Keyword(s):  
Cell Proliferation ◽  
Current Knowledge ◽  
Cell Cycle Control ◽  
Peroxisome Proliferator ◽  
Oncogenic Signaling ◽  
Peroxisome Proliferator Activated Receptor ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Oncogenic Signaling Pathways

Peroxisome proliferator-activated receptor-β/δ(PPARβ/δ) is a ligand-activated transcription factor with essential functions in the regulation of lipid catabolism, glucose homeostasis, and inflammation, which makes it a potentially relevant drug target for the treatment of major human diseases. In addition, there is strong evidence that PPARβ/δmodulates oncogenic signaling pathways and tumor growth. Consistent with these observations, numerous reports have clearly documented a role for PPARβ/δin cell cycle control, differentiation, and apoptosis. However, the precise role of PPARβ/δin tumorigenesis and cell proliferation remains controversial. This review summarizes our current knowledge and proposes a model corroborating the discrepant data in this area of research.

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