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Articles by Bart Staels
Intestinal FXR deficiency uncouples steatosis protection from liver inflammation and fibrosis in MASH-diet fed mice
Abstract The Farnesoid X Receptor (FXR), a nuclear bile acid (BA) receptor highly expressed in the liver and intestine, is a potential pharmacological target for Metabolic dysfunction-Associated SteatoHepatitis (MASH). While intestinal FXR inhibition reduces high-fat diet (HFD)-induced hepatic steatosis, its role in MASH progression remains unclear. This study investigates the impact of intestinal FXR-deficiency on MASH development in a diet-induced murine model.
A functional variant in the porcine APOA2 promoter alters hepatic gene expression via RORα
Abstract Apolipoprotein A2 is the second most abundant protein in high-density lipoproteins and plays an important role in lipid and glucose metabolism. APOA2 has been identified as a candidate gene influencing fat-related traits in pigs, and genetic variation has been associated with its hepatic expression. The aim of this study was to identify regulatory polymorphisms in the APOA2 promoter and assess their impact on gene expression.
Partitioned polygenic scores show mechanistic heterogeneity in type 2 diabetes and hypertension comorbidity - Nature Communications
Abstract Type 2 diabetes and hypertension are common health conditions that often occur together, suggesting shared biological mechanisms. To explore this relationship, we analyse large-scale multiomic data to uncover genetic factors underlying type 2 diabetes and blood pressure comorbidity.
Trajectory analysis of hepatic stellate cell differentiation reveals metabolic regulation of cell commitment and fibrosis - Nature Communications
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Abstract Defining the trajectory of cells during differentiation and disease is key for uncovering the mechanisms driving cell fate and identity. However, trajectories of human cells remain largely unexplored due to the challenges of studying them with human samples.
By Albert Blasco-Roset, Joan Pera, Damia Romero-Moya, Celia Sanchez, Andrew McQuillin, Marsha Y. Morgan, Nuria Montserrat, Bart Staels, Maria L Martínez-Chantar, Felix Elortza, Antonio Zorzano, Silvia Affo, Raquel Ferrer-Lorente, Maria Mercado-Gómez, Alessandra Giorgetti, Marta Varela-Rey, Ashwin Woodhoo
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Nature
Verified
Rev-erb-α antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice
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Keywords respiratory bacterial infection aging circadian rhythm Rev-erb-α apelin Streptococcus pneumoniae apelin receptor alveolar macrophages Research topics CP: Microbiology CP: Immunology Introduction Immune-function dysregulation has a major impact on age-related diseases, with an elevation in the risk of cancer and cardiovascular, metabolic, and neurodegenerative pathologies.
By Fabiola Angulo, Claudine Joseph, Lou Delval, Séverine Heumel, Patricia Rodrigues, Valentin Sencio, Tom Bourguignon, Sophie Salomé-Desnoulez, Isabelle Wolowczuk, Jean-Claude Sirard, Muriel Pichavant, Bart Staels, Joel Haas Verified, Ruxandra Gref, Jimmy Vandel, Arnaud Machelart, Hélène Duez, Benoit POURCET, François Trottein, Lucie Deruyter, Marie Bicharel, Marina Gomes Machado, Marie Fourcot, Stéphane Delhaye, Philippe Valet, Serge Adnot
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Cell Reports
Verified
Data-driven cluster analysis identifies distinct types of metabolic dysfunction-associated steatotic liver disease - Nature Medicine
Abstract Metabolic dysfunction-associated steatotic liver disease (MASLD) exhibits considerable variability in clinical outcomes. Identifying specific phenotypic profiles within MASLD is essential for developing targeted therapeutic strategies. Here we investigated the heterogeneity of MASLD using partitioning around medoids clustering based on six simple clinical variables in a cohort of 1,389 individuals living with obesity.
Increased O-GlcNAcylation connects metabolic to transcriptional reprogramming during pathophysiological cell activation
Keywords O-GlcNAcylation pathophysiological cell activation transcriptional reprogramming metabolic reprogramming transcriptional regulators chronic diseases Get full text access Log in, subscribe or purchase for full access. References 1. Makwana, V. ... Essential role of O-GlcNAcylation in stabilization of oncogenic factors Biochim. Biophys. Acta Gen. Subj. 2019; 1863:1302-1317 2. Shyer, J.A. ... Metabolic signaling in T cells Cell Res. 2020; 30:649-659 3. Henderson, J. ∙ O’Reilly, S.
Adipose tissue macrophage infiltration and hepatocyte stress increase GDF-15 throughout development of obesity to MASH - Nature Communications
Abstract Plasma growth differentiation factor-15 (GDF-15) levels increase with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) but the underlying mechanism remains poorly defined.
Nuclear receptors: pathophysiological mechanisms and drug targets in liver disease
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Nuclear receptors: pathophysiological mechanisms and drug targets in liver disease
Recent advances in basic science Nuclear receptors: pathophysiological mechanisms and drug targets in liver disease Statistics from Altmetric.com Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.
O-GlcNAcylation controls pro-fibrotic transcriptional regulatory signaling in myofibroblasts - Cell Death & Disease
Abstract Tissue injury causes activation of mesenchymal lineage cells into wound-repairing myofibroblasts (MFs), whose uncontrolled activity ultimately leads to fibrosis. Although this process is triggered by deep metabolic and transcriptional reprogramming, functional links between these two key events are not yet understood.
Genetic Factors Altering Immune Responses in Atrial Fibrillation: JACC Review Topic of the Week
References 1. "2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): the Task Force for the Diagnosis and Management of Atrial Fibrillation of the European Society of Cardiology (ESC) developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC". Eur Heart J . 2021;42:373-498. 2.
Functional genomics uncovers the transcription factor BNC2 as required for myofibroblastic activation in fibrosis - Nature Communications
Abstract Tissue injury triggers activation of mesenchymal lineage cells into wound-repairing myofibroblasts, whose unrestrained activity leads to fibrosis. Although this process is largely controlled at the transcriptional level, whether the main transcription factors involved have all been identified has remained elusive. Here, we report multi-omics analyses unraveling Basonuclin 2 (BNC2) as a myofibroblast identity transcription factor.
GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice - Nature Metabolism
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Abstract Dual agonists activating the peroxisome proliferator-activated receptors alpha and gamma (PPARɑ/ɣ) have beneficial effects on glucose and lipid metabolism in patients with type 2 diabetes, but their development was discontinued due to potential adverse effects. Here we report the design and preclinical evaluation of a molecule that covalently links the PPARɑ/ɣ dual-agonist tesaglitazar to a GLP-1 receptor agonist (GLP-1RA) to allow for GLP-1R-dependent cellular delivery of tesaglitazar.
By Carmelo Quarta, Mostafa Bakhti, Christoffer Clemmensen, Daniel J. Drucker, Cristina García-Cáceres, Stephan Herzig, Susanna M. Hofmann, Heiko Lickert, Diego Perez-Tilve, Bart Staels, Richard D. DiMarchi, Matthias H. Tschöp, Brian Finan, Timo Müller, Aaron Novikoff, Arek Liskiewicz, Daniela Liskiewicz
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Nature
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Hepatic sexual dimorphism — implications for non-alcoholic fatty liver disease - Nature Reviews Endocrinology
Abstract The liver is often thought of as a single functional unit, but both its structural and functional architecture make it highly multivalent and adaptable. In any given physiological situation, the liver can maintain metabolic homeostasis, conduct appropriate inflammatory responses, carry out endobiotic and xenobiotic transformation and synthesis reactions, as well as store and release multiple bioactive molecules. Moreover, the liver is a very resilient organ.
PPAR control of metabolism and cardiovascular functions
1. WHO. Cardiovascular diseases (CVDs). https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) (2017). 2. Staels, B., Maes, M. & Zambon, A. Fibrates and future PPARalpha agonists in the treatment of cardiovascular disease. Nat. Clin. Pract. Cardiovasc. Med. 5, 542–553 (2008). CAS PubMed Article PubMed Central Google Scholar 3. Gross, B., Pawlak, M., Lefebvre, P. & Staels, B. PPARs in obesity-induced T2DM, dyslipidaemia and NAFLD. Nat. Rev. Endocrinol. 13, 36–49 (2017).
GIANT: galaxy-based tool for interactive analysis of transcriptomic data
Abstract Transcriptomic analyses are broadly used in biomedical research calling for tools allowing biologists to be directly involved in data mining and interpretation. We present here GIANT, a Galaxy-based tool for Interactive ANalysis of Transcriptomic data, which consists of biologist-friendly tools dedicated to analyses of transcriptomic data from microarray or RNA-seq analyses.
Perspectives on the use of super-enhancers as a defining feature of cell/tissue-identity genes
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Microbiome Modulation of the Host Adaptive Immunity through Bile Acid Modification
The microbiome is well known to influence the immune response of the host. Song et al. now show that the microbiome modulates adaptive immunity in mice through formation of bile acid species acting on RORγ + regulatory T cells via the Vitamin D Receptor, thereby lowering the vulnerability for chemically induced colitis.
The nuclear receptor FXR inhibits Glucagon-Like Peptide-1 secretion in response to microbiota-derived Short-Chain Fatty Acids
Abstract The gut microbiota participates in the control of energy homeostasis partly through fermentation of dietary fibers hence producing short-chain fatty acids (SCFAs), which in turn promote the secretion of the incretin Glucagon-Like Peptide-1 (GLP-1) by binding to the SCFA receptors FFAR2 and FFAR3 on enteroendocrine L-cells. We have previously shown that activation of the nuclear Farnesoid X Receptor (FXR) decreases the L-cell response to glucose.
Understanding lipid metabolism through hepatic steat-omics
Alterations in lipid metabolism are closely linked to disorders such as cardiovascular disease, type 2 diabetes mellitus and non-alcoholic fatty liver disease. A multi-omics study on a mouse genetic reference panel uncovers regulatory networks and potential biomarkers of hepatic lipid metabolism. Access optionsAccess options Subscribe to Journal Get full journal access for 1 year $213.00 only $17.75 per issue All prices are NET prices. VAT will be added later in the checkout.
Fasting the Microbiota to Improve Metabolism?
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