scholarly journals COUP-TFII in Health and Disease

Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 101 ◽  
Author(s):  
Simone Polvani ◽  
Sara Pepe ◽  
Stefano Milani ◽  
Andrea Galli

The nuclear receptors (NRs) belong to a vast family of evolutionary conserved proteins acting as ligand-activated transcription factors. Functionally, NRs are essential in embryogenesis and organogenesis and in adulthood they are involved in almost every physiological and pathological process. Our knowledge of NRs action has greatly improved in recent years, demonstrating that both their expression and activity are tightly regulated by a network of signaling pathways, miRNA and reciprocal interactions. The Chicken Ovalbumin Upstream Promoter Transcription Factor II (COUP-TFII, NR2F2) is a NR classified as an orphan due to the lack of a known natural ligand. Although its expression peaks during development, and then decreases considerably, in adult tissues, COUP-TFII is an important regulator of differentiation and it is variably implicated in tissues homeostasis. As such, alterations of its expression or its transcriptional activity have been studied and linked to a spectrum of diseases in organs and tissues of different origins. Indeed, an altered COUP-TFII expression and activity may cause infertility, abnormality in the vascular system and metabolic diseases like diabetes. Moreover, COUP-TFII is actively investigated in cancer research but its role in tumor progression is yet to be fully understood. In this review, we summarize the current understanding of COUP-TFII in healthy and pathological conditions, proposing an updated and critical view of the many functions of this NR.

2018 ◽  
Vol 315 (1) ◽  
pp. E15-E28 ◽  
Author(s):  
Amita Bansal ◽  
Rebecca A. Simmons

The incidence of metabolic disorders like type 2 diabetes (T2D) and obesity continue to increase. Although it is evident that the increasing incidence of diabetes confers a global societal and economic burden, the mechanisms responsible for the increased incidence of T2D are not well understood. Extensive efforts to understand the association of early-life perturbations with later onset of metabolic diseases, the founding principle of developmental origins of health and disease, have been crucial in determining the mechanisms that may be driving the pathogenesis of T2D. As the programming of the epigenome occurs during critical periods of development, it has emerged as a potential molecular mechanism that could occur early in life and impact metabolic health decades later. In this review, we critically evaluate human and animal studies that illustrated an association of epigenetic processes with development of T2D as well as intervention strategies that have been employed to reverse the perturbed epigenetic modification or reprogram the naturally occurring epigenetic marks to favor improved metabolic outcome. We highlight that although our understanding of epigenetics and its contribution toward developmental origins of T2D continues to grow, whether epigenetics is a cause, consequence, or merely a correlation remains debatable due to the many limitations/challenges of the existing epigenetic studies. Finally, we discuss the potential of establishing collaborative research efforts between different disciplines, including physiology, epigenetics, and bioinformatics, to help advance the developmental origins field with great potential for understanding the pathogenesis of T2D and developing preventive strategies for T2D.


2014 ◽  
Vol 21 (19) ◽  
pp. 2190-2207 ◽  
Author(s):  
S. Schildge ◽  
C. Bohrer ◽  
S. Pfurr ◽  
K. Mammadzada ◽  
K. Schachtrup ◽  
...  

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 850
Author(s):  
María Ángeles Martín ◽  
Sonia Ramos

Flavanols are natural occurring polyphenols abundant in fruits and vegetables to which have been attributed to beneficial effects on health, and also against metabolic diseases, such as diabetes, obesity and metabolic syndrome. These positive properties have been associated to the modulation of different molecular pathways, and importantly, to the regulation of immunological reactions (pro-inflammatory cytokines, chemokines, adhesion molecules, nuclear factor-κB [NF-κB], inducible enzymes), and the activity of cells of the immune system. In addition, flavanols can modulate the composition and function of gut microbiome in a prebiotic-like manner, resulting in the positive regulation of metabolic pathways and immune responses, and reduction of low-grade chronic inflammation. Moreover, the biotransformation of flavanols by gut bacteria increases their bioavailability generating a number of metabolites with potential to affect human metabolism, including during metabolic diseases. However, the exact mechanisms by which flavanols act on the microbiota and immune system to influence health and disease remain unclear, especially in humans where these connections have been scarcely explored. This review seeks to summarize recent advances on the complex interaction of flavanols with gut microbiota, immunity and inflammation focus on metabolic diseases.


PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Marion Peyrou ◽  
Pierluigi Ramadori ◽  
Lucie Bourgoin ◽  
Michelangelo Foti

Peroxisome-proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that exert in the liver a transcriptional activity regulating a whole spectrum of physiological functions, including cholesterol and bile acid homeostasis, lipid/glucose metabolism, inflammatory responses, regenerative mechanisms, and cell differentiation/proliferation. Dysregulations of the expression, or activity, of specific PPAR isoforms in the liver are therefore believed to represent critical mechanisms contributing to the development of hepatic metabolic diseases, disorders induced by hepatic viral infections, and hepatocellular adenoma and carcinoma. In this regard, specific PPAR agonists have proven to be useful to treat these metabolic diseases, but for cancer therapies, the use of PPAR agonists is still debated. Interestingly, in addition to previously described mechanisms regulating PPARs expression and activity, microRNAs are emerging as new important regulators of PPAR expression and activity in pathophysiological conditions and therefore may represent future therapeutic targets to treat hepatic metabolic disorders and cancers. Here, we reviewed the current knowledge about the general roles of the different PPAR isoforms in common chronic metabolic and infectious liver diseases, as well as in the development of hepatic cancers. Recent works highlighting the regulation of PPARs by microRNAs in both physiological and pathological situations with a focus on the liver are also discussed.


Proceedings ◽  
2020 ◽  
Vol 61 (1) ◽  
pp. 10
Author(s):  
Carles Rosés ◽  
Amanda Cuevas-Sierra ◽  
Salvador Quintana ◽  
José I. Riezu-Boj ◽  
J. Alfredo Martínez ◽  
...  

The Mediterranean diet (MD) is recognised as one of the healthiest diets worldwide and is associated with the prevention of cardiovascular and metabolic diseases, among others. Dietary habits are considered one of the strongest modulators of the gut microbiota, which seems to play a significant role in the health and disease of the host. The purpose of the present study was to evaluate interactive associations between gut microbiota composition and habitual dietary intake in 360 Spanish adults of the Obekit cohort (normal weight, overweight and obese subjects). Dietary intake and adherence to the MD tests together with faecal samples were collected from each subject. Faecal 16S rRNA sequencing was performed and checked against the dietary habits. MetagenomeSeq was the statistical tool applied to analyse at the species taxonomic level. Results from this study confirm that a strong adherence to the MD increases the population of some beneficial bacteria, improving microbiota status towards a healthier pattern. Bifidobacterium animalis is the species with the strongest association with the MD. One of the highlights is the positive association between several SCFA-producing bacteria and high adherence to the MD. In conclusion, this study shows that MD, fibre, legumes, vegetables, fruit and nuts intakes are associated with an increase in butyrate-producing taxa such as Roseburia faecis, Ruminococcus bromii and Oscillospira (Flavonifractor) plautii.


2014 ◽  
Vol 38 (2) ◽  
pp. 170-175 ◽  
Author(s):  
Jamie R. Mitchell ◽  
Jiun-Jr Wang

Dr. Carl Wiggers' careful observations have provided a meaningful resource for students to learn how the heart works. Throughout the many years from his initial reports, the Wiggers diagram has been used, in various degrees of complexity, as a fundamental tool for cardiovascular instruction. Often, the various electrical and mechanical plots are the novice learner's first exposure to simulated data. As the various temporal relationships throughout a heartbeat could simply be memorized, the challenge for the cardiovascular instructor is to engage the learner so the underlying mechanisms governing the changing electrical and mechanical events are truly understood. Based on experience, we suggest some additions to the Wiggers diagram that are not commonly used to enhance cardiovascular pedagogy. For example, these additions could be, but are not limited to, introducing the concept of energy waves and their role in influencing pressure and flow in health and disease. Also, integrating concepts of exercise physiology, and the differences in cardiac function and hemodynamics between an elite athlete and normal subject, can have a profound impact on student engagement. In describing the relationship between electrical and mechanical events, the instructor may find the introduction of premature ventricular contractions as a useful tool to further understanding of this important principle. It is our hope that these examples can aid cardiovascular instructors to engage their learners and promote fundamental understanding at the expense of simple memorization.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1208 ◽  
Author(s):  
Michael J. Garabedian ◽  
Charles A. Harris ◽  
Freddy Jeanneteau

Glucocorticoids via the glucocorticoid receptor (GR) have effects on a variety of cell types, eliciting important physiological responses via changes in gene expression and signaling. Although decades of research have illuminated the mechanism of how this important steroid receptor controls gene expression using in vitro and cell culture–based approaches, how GR responds to changes in external signals in vivo under normal and pathological conditions remains elusive. The goal of this review is to highlight recent work on GR action in fat cells and liver to affect metabolism in vivo and the role GR ligands and receptor phosphorylation play in calibrating signaling outputs by GR in the brain in health and disease. We also suggest that both the brain and fat tissue communicate to affect physiology and behavior and that understanding this “brain-fat axis” will enable a more complete understanding of metabolic diseases and inform new ways to target them.


2016 ◽  
Vol 473 (16) ◽  
pp. 2439-2452 ◽  
Author(s):  
Chrisostomos Prodromou

Heat shock protein 90 (Hsp90) is a molecular chaperone that is involved in the activation of disparate client proteins. This implicates Hsp90 in diverse biological processes that require a variety of co-ordinated regulatory mechanisms to control its activity. Perhaps the most important regulator is heat shock factor 1 (HSF1), which is primarily responsible for upregulating Hsp90 by binding heat shock elements (HSEs) within Hsp90 promoters. HSF1 is itself subject to a variety of regulatory processes and can directly respond to stress. HSF1 also interacts with a variety of transcriptional factors that help integrate biological signals, which in turn regulate Hsp90 appropriately. Because of the diverse clientele of Hsp90 a whole variety of co-chaperones also regulate its activity and some are directly responsible for delivery of client protein. Consequently, co-chaperones themselves, like Hsp90, are also subject to regulatory mechanisms such as post translational modification. This review, looks at the many different levels by which Hsp90 activity is ultimately regulated.


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