PPARs and Female Reproduction: Evidence from  Genetically Manipulated Mice

Yang, Jichun; Zhang, Xiaoyan; Zhou, Yunfeng; Zhang, Dongjuan; Huo, Ming; Guan, Youfei

doi:10.1155/2008/723243

Cited by 31 publications

(25 citation statements)

References 79 publications

(106 reference statements)

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“…Significant androgen binding in adipose tissue (and adipocytes) has long been established (155)(156)(157)(158)(159)(160)(161). These findings are supported by our own analyses of fat tissue steroid content and androgen-receptor expression (162,163).…”

Section: Androgenssupporting

confidence: 73%

Diabetes in Women

Tsatsoulis¹,

Wyckoff²,

Brown³

2010

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), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is for-bidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights.Printed on acid-free paper PrefaceThis book is devoted to women with diabetes and to women at risk of diabetes. The primary aim is to provide up-to-date information on current topics pertaining to diabetes and cardiometabolic risk in women throughout the lifecycle.The concept behind this book arises from the understanding that gender differences impact the pathophysiology and clinical burden of diabetes in women. The fundamental differences between men and women are primarily attributed to sex hormones, which define not only the sexually dimorphic traits but also play an important role in regulating energy metabolism, body composition, and vascular function.The book is structured into five main sections with a total of 23 chapters. The first section, "Sex Differences in Cardiometabolic Risk", reviews the differences between the sexes in energy balance and body composition, the impact of menopause on these parameters, and the clinical expression and burden of cardiovascular disease in women with diabetes. There is also special reference to the cardiometabolic risk in women with PCOS and the concept of fetal programming of PCOS by androgen excess. Section 2 focuses on the "Impact of Diabetes on Women's Health". It includes a chapter that explores the impact of poverty and globalization on the emerging epidemic of obesity in developing countries. Other chapters review depression, eating disorders, sexual health, and contraception in women with diabetes. Fertility and pregnancy in women with PCOS is also reviewed with a special focus on the metabolic aspects of the syndrome. "Diabetes and Pregnancy" is covered in Section 3. The diagnosis and treatment of gestational diabetes, nutrition in pregnancy, prepregnancy counseling, obstetrical and medical care of women with diabetes, preeclampsia, and the use of ultrasound in the management of gestational and preexisting diabetes in pregnancy are reviewed. The increasing burden of diabetes and gestational diabetes in developing nations is highlighted in Chapter 12. Section 4 is devoted to the "Offspring of the Diabetic Mother", and reviews the phenomenon of metabolic imprinting as well as the genetic basis of the various forms of diabetes and the issue of breastfeeding. Lastly, Section 5 summarizes in a chapter "The Disease Management of Women with Diabetes".The book Diabetes in Women is meant for physicians with an interest in diabetes: endocrinologists, obstetricians, and gynecologists, generalists as well as medical students and those training in these areas of h...

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Section: Androgenssupporting

confidence: 73%

Diabetes in Women

Tsatsoulis¹,

Wyckoff²,

Brown³

2010

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“…The high expression of PPARG in atherosclerotic lesions has fostered intensive research efforts to identify possible roles of PPARG in regulating cholesterol influx, thereby promoting the development of atherosclerosis [64,65]. During reproduction, PPARG is involved in secretion of reproductive hormones by trophoblasts, and it has been suggested to negatively regulate trophoblast invasion into the decidua [66,67].…”

Section: Ppars In Animal Modelsmentioning

confidence: 99%

Nuclear Receptors of the Peroxisome Proliferator-Activated Receptor (PPAR) Family in Gestational Diabetes: From Animal Models to Clinical Trials1

Arck

Tóth

Pestka

et al. 2010

Biology of Reproduction

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Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance and affects 2%-8% of all pregnancies. Among other complications, GDM can lead to the development of type 2 diabetes mellitus (DM 2) in both mother and child. Peroxisome proliferator-activated receptors (PPARs) are major regulators of glucose and lipid metabolism. Furthermore, PPARs are mediators of inflammation and angiogenesis and are involved in the maternal adaptational dynamics during pregnancy to serve the requirements of the growing fetus. PPARs were originally named for their ability to induce hepatic peroxisome proliferation in mice in response to xenobiotic stimuli. The expression of three PPAR isoforms, alpha, beta/delta, and gamma, have been described. Each of them is encoded by different genes; however, they share 60%-80% homology in their ligand-binding and DNA-binding domains. PPARs are involved in trophoblast differentiation, invasion, metabolism, and parturition and are expressed in invasive extravillous trophoblast and villous trophoblast cells. Nuclear receptors, to which PPARs belong, are promising targets for disease-specific treatment strategies because they act as transcription factors controlling cellular processes at the level of gene expression and may produce selective alterations in downstream gene expression. To date, PPAR agonists are therapeutically used in patients with DM 2 and in patients with reproductive disorders such as polycystic ovary syndrome. Because of safety concerns and limited data, PPAR agonists are not yet included in GDM-related treatment strategies. Our objective herein is to review newly emerging generations of selective PPAR modulators and panagonists, which may have potent therapeutic implications in the context of GDM.

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“…50,63 Interestingly, a role for PPARa in mammalian female reproduction has been revealed recently, 64 and in ovariectomized rats Fenofibrate helps maintain bone-mass. 65 Given this context, and accruing evidence that reproductive signals alter lifespan of diverse species, it is enticing to speculate if PPARa and other NHRs may influence vertebrate longevity. Since molecular dissection of metabolic pathways is challenging in mammalian systems, understanding how NHR-49/PPARa and its partners promote C. elegans longevity is likely to provide new mechanistic insights and therapeutic targets for regulating lipid homeostasis and aging in humans.…”

Section: Feedback Loops and Nhr Partnerships Triggered By Germline Simentioning

confidence: 99%

Nuclear hormone receptors as mediators of metabolic adaptability following reproductive perturbations

Ratnappan

Ward

Ghazi

2016

Worm

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Previously, we identified a group of nuclear hormone receptors (NHRs) that promote longevity in the nematode Caenorhabditis elegans following germline-stem cell (GSC) loss. This group included NHR-49, the worm protein that performs functions similar to vertebrate PPARa, a key regulator of lipid metabolism. We showed that NHR-49/PPARa enhances mitochondrial b-oxidation and fatty acid desaturation upon germline removal, and through the coordinated enhancement of these processes allows the animal to retain lipid homeostasis and undergo lifespan extension. NHR-49/ PPARa expression is elevated in GSC-ablated animals, in part, by DAF-16/FOXO3A and TCER-1/ TCERG1, two other conserved, pro-longevity transcriptional regulators that are essential for germline-less longevity. In exploring the roles of the other pro-longevity NHRs, we discovered that one of them, NHR-71/HNF4, physically interacted with NHR-49/PPARa. NHR-71/HNF4 did not have a broad impact on the expression of b-oxidation and desaturation targets of NHR-49/PPARa. But, both NHR-49/PPARa and NHR-71/HNF4 were essential for the increased expression of DAF-16/ FOXO3A-and TCER-1/TCERG1-downstream target genes. In addition, nhr-49 inactivation caused a striking membrane localization of KRI-1, the only known common upstream regulator of DAF-16/ FOXO3A and TCER-1/TCERG1, suggesting that it may operate in a positive feedback loop to potentiate the activity of this pathway. These data underscore how selective interactions between NHRs that function as nodes in metabolic networks, confer functional specificity in response to different physiological stimuli.

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PPARs and Female Reproduction: Evidence from Genetically Manipulated Mice

Cited by 31 publications

References 79 publications

Diabetes in Women

Diabetes in Women

Nuclear Receptors of the Peroxisome Proliferator-Activated Receptor (PPAR) Family in Gestational Diabetes: From Animal Models to Clinical Trials1

Nuclear hormone receptors as mediators of metabolic adaptability following reproductive perturbations

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