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Kristina schoonjans

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https://www.readbyqxmd.com/read/29662071/lrh-1-agonism-favours-an-immune-islet-dialogue-which-protects-against-diabetes-mellitus
#1
Nadia Cobo-Vuilleumier, Petra I Lorenzo, Noelia García Rodríguez, Irene de Gracia Herrera Gómez, Esther Fuente-Martin, Livia López-Noriega, José Manuel Mellado-Gil, Silvana-Yanina Romero-Zerbo, Mathurin Baquié, Christian Claude Lachaud, Katja Stifter, German Perdomo, Marco Bugliani, Vincenzo De Tata, Domenico Bosco, Geraldine Parnaud, David Pozo, Abdelkrim Hmadcha, Javier P Florido, Miguel G Toscano, Peter de Haan, Kristina Schoonjans, Luis Sánchez Palazón, Piero Marchetti, Reinhold Schirmbeck, Alejandro Martín-Montalvo, Paolo Meda, Bernat Soria, Francisco-Javier Bermúdez-Silva, Luc St-Onge, Benoit R Gauthier
Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis...
April 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29656109/bile-acids-are-important-direct-and-indirect-regulators-of-the-secretion-of-appetite-and-metabolism-regulating-hormones-from-the-gut-and-pancreas
#2
Rune E Kuhre, Nicolai J Wewer Albrechtsen, Olav Larsen, Sara L Jepsen, Emilie Balk-Møller, Daniel B Andersen, Carolyn F Deacon, Kristina Schoonjans, Frank Reimann, Fiona M Gribble, Reidar Albrechtsen, Bolette Hartmann, Mette M Rosenkilde, Jens J Holst
OBJECTIVE: Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. METHODS: The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose...
May 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29443959/transcriptional-regulation-by-nr5a2-links-differentiation-and-inflammation-in-the-pancreas
#3
Isidoro Cobo, Paola Martinelli, Marta Flández, Latifa Bakiri, Mingfeng Zhang, Enrique Carrillo-de-Santa-Pau, Jinping Jia, Víctor J Sánchez-Arévalo Lobo, Diego Megías, Irene Felipe, Natalia Del Pozo, Irene Millán, Liv Thommesen, Torunn Bruland, Sara H Olson, Jill Smith, Kristina Schoonjans, William R Bamlet, Gloria M Petersen, Núria Malats, Laufey T Amundadottir, Erwin F Wagner, Francisco X Real
Chronic inflammation increases the risk of developing one of several types of cancer. Inflammatory responses are currently thought to be controlled by mechanisms that rely on transcriptional networks that are distinct from those involved in cell differentiation. The orphan nuclear receptor NR5A2 participates in a wide variety of processes, including cholesterol and glucose metabolism in the liver, resolution of endoplasmic reticulum stress, intestinal glucocorticoid production, pancreatic development and acinar differentiation...
February 22, 2018: Nature
https://www.readbyqxmd.com/read/29404496/megatrends-in-bile-acid-receptor-research
#4
Luciano Adorini, Kristina Schoonjans, Scott L Friedman
No abstract text is available yet for this article.
October 2017: Hepatology Communications
https://www.readbyqxmd.com/read/29379893/the-orphan-nuclear-receptor-liver-homolog-receptor-1-nr5a2-regulates-ovarian-granulosa-cell-proliferation
#5
Marie-Charlotte Meinsohn, Fanny Morin, Kalyne Bertolin, Raj Duggavathi, Kristina Schoonjans, Bruce D Murphy
In mouse ovaries, liver receptor homolog-1 [nuclear receptor subfamily 5, group A, member 2 (Nr5a2)] expression is restricted to granulosa cells. Mice with Nr5a2 depletion in this cell population fail to ovulate. To determine whether Nr5a2 is essential for granulosa cell proliferation during follicular maturation, we generated granulosa-specific conditional knockout mice (genotype Nr5a2 floxed Cre-recombinase driven by the anti-Müllerian type II receptor, hereafter cKO) with Nr5a2 depletion from primary follicles forward...
January 1, 2018: Journal of the Endocrine Society
https://www.readbyqxmd.com/read/29339725/tgr5-signalling-promotes-mitochondrial-fission-and-beige-remodelling-of-white-adipose-tissue
#6
Laura A Velazquez-Villegas, Alessia Perino, Vera Lemos, Marika Zietak, Mitsunori Nomura, Thijs Willem Hendrik Pols, Kristina Schoonjans
Remodelling of energy storing white fat into energy expending beige fat could be a promising strategy to reduce adiposity. Here, we show that the bile acid-responsive membrane receptor TGR5 mediates beiging of the subcutaneous white adipose tissue (scWAT) under multiple environmental cues including cold exposure and prolonged high-fat diet feeding. Moreover, administration of TGR5-selective bile acid mimetics to thermoneutral housed mice leads to the appearance of beige adipocyte markers and increases mitochondrial content in the scWAT of Tgr5 +/+ mice but not in their Tgr5 -/- littermates...
January 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29199021/an-integrated-systems-genetics-and-omics-toolkit-to-probe-gene-function
#7
Hao Li, Xu Wang, Daria Rukina, Qingyao Huang, Tao Lin, Vincenzo Sorrentino, Hongbo Zhang, Maroun Bou Sleiman, Danny Arends, Aaron McDaid, Peiling Luan, Naveed Ziari, Laura A Velázquez-Villegas, Karim Gariani, Zoltan Kutalik, Kristina Schoonjans, Richard A Radcliffe, Pjotr Prins, Stephan Morgenthaler, Robert W Williams, Johan Auwerx
Identifying genetic and environmental factors that impact complex traits and common diseases is a high biomedical priority. Here, we developed, validated, and implemented a series of multi-layered systems approaches, including (expression-based) phenome-wide association, transcriptome-/proteome-wide association, and (reverse-) mediation analysis, in an open-access web server (systems-genetics.org) to expedite the systems dissection of gene function. We applied these approaches to multi-omics datasets from the BXD mouse genetic reference population, and identified and validated associations between genes and clinical and molecular phenotypes, including previously unreported links between Rpl26 and body weight, and Cpt1a and lipid metabolism...
January 24, 2018: Cell Systems
https://www.readbyqxmd.com/read/28853753/a-multiscale-study-of-the-role-of-dynamin-in-the-regulation-of-glucose-uptake
#8
Raphaël Trouillon, M Cristina Letizia, Keir J Menzies, Laurent Mouchiroud, Johan Auwerx, Kristina Schoonjans, Martin A M Gijs
Glucose uptake in muscle cells in response to insulin is a fundamental mechanism for metabolism. The inability of cells to mobilize the specific glucose transporter GLUT4 is believed to be at least partially accountable for diseases, like diabetes, where cells do not respond to an insulin stimulus. In this work, a microchip is used to detect electrochemically glucose uptake from C2C12 myoblasts cultured on a patch of paper upon exposure to insulin. More importantly, the data suggest a new role for dynamin, a molecular motor which would be involved in GLUT4 translocation by facilitating exocytosis...
October 16, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28586124/small-heterodimer-partner-deletion-prevents-hepatic-steatosis-and-when-combined-with-farnesoid-x-receptor-loss-protects-against-type-2-diabetes-in-mice
#9
Oludemilade Akinrotimi, Ryan Riessen, Philip VanDuyne, Jung Eun Park, Yoon Kwang Lee, Lee-Jun Wong, Ann M Zavacki, Kristina Schoonjans, Sayeepriyadarshini Anakk
Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are important regulators of bile acid, lipid, and glucose homeostasis. Here, we show that global Fxr-/- Shp-/- double knockout (DKO) mice are refractory to weight gain, glucose intolerance, and hepatic steatosis when challenged with high-fat diet. DKO mice display an inherently increased capacity to burn fat and suppress de novo hepatic lipid synthesis. Moreover, DKO mice were also very active and that correlated well with the observed increase in phosphoenolpyruvate carboxykinase expression, type IA fibers, and mitochondrial function in skeletal muscle...
December 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28520915/ovary-specific-depletion-of-the-nuclear-receptor-nr5a2-compromises-expansion-of-the-cumulus-oophorus-but-not-fertilization-by-intracytoplasmic-sperm-injection
#10
Kalyne Bertolin, Marie-Charlotte Meinsohn, João Suzuki, Jan Gossen, Kristina Schoonjans, Rajesha Duggavathi, Bruce D Murphy
The orphan nuclear receptor, liver receptor homolog-1 (aka Nuclear receptor subfamily 5, Group A, Member 2 (Nr5a2)), is widely expressed in mammalian tissues, and its ovarian expression is restricted to granulosa cells of activated follicles. We employed the floxed Nr5a2 (Nr5a2f/f) mutant mouse line and two granulosa-specific Cre lines, Anti-Müllerian hormone receptor- 2 (Amhr2Cre) and transgenic cytochrome P450 family 19 subfamily A polypeptide 1 (tgCyp19Cre), to develop two tissue- and time-specific Nr5a2 depletion models: Nr5a2Amhr2-/- and Nr5a2Cyp19-/-...
June 1, 2017: Biology of Reproduction
https://www.readbyqxmd.com/read/28487283/bile-acids-deoxycholic-acid-and-ursodeoxycholic-acid-differentially-regulate-human-%C3%AE-defensin-1-and-2-secretion-by-colonic-epithelial-cells
#11
Natalia K Lajczak, Vinciane Saint-Criq, Aoife M O'Dwyer, Alessia Perino, Luciano Adorini, Kristina Schoonjans, Stephen J Keely
Bile acids and epithelial-derived human β-defensins (HβDs) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic HβD expression and aimed to test this by investigating the effects of deoxycholic acid (DCA) and ursodeoxycholic acid on the expression and release of HβD1 and HβD2 from colonic epithelial cells and mucosal tissues. DCA (10-150 µM) stimulated the release of both HβD1 and HβD2 from epithelial cell monolayers and human colonic mucosal tissue in vitro In contrast, ursodeoxycholic acid (50-200 µM) inhibited both basal and DCA-induced defensin release...
September 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28422755/%C3%AE-klotho-deficiency-protects-against-obesity-through-a-crosstalk-between-liver-microbiota-and-brown-adipose-tissue
#12
Emmanuel Somm, Hugues Henry, Stephen J Bruce, Sébastien Aeby, Marta Rosikiewicz, Gerasimos P Sykiotis, Mohammed Asrih, François R Jornayvaz, Pierre Damien Denechaud, Urs Albrecht, Moosa Mohammadi, Andrew Dwyer, James S Acierno, Kristina Schoonjans, Lluis Fajas, Gilbert Greub, Nelly Pitteloud
β-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb-/- mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we investigated the energy homeostasis in Klb-/- mice on high-fat diet in order to better understand the consequences of abrogating both endogenous FGF15/19 and FGF21 signaling during caloric overload. Surprisingly, Klb-/- mice are resistant to diet-induced obesity (DIO) owing to enhanced energy expenditure and BAT activity...
April 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28094767/impaired-sumoylation-of-nuclear-receptor-lrh-1-promotes-nonalcoholic-fatty-liver-disease
#13
Sokrates Stein, Vera Lemos, Pan Xu, Hadrien Demagny, Xu Wang, Dongryeol Ryu, Veronica Jimenez, Fatima Bosch, Thomas F Lüscher, Maaike H Oosterveer, Kristina Schoonjans
Hepatic steatosis is caused by metabolic imbalances that could be explained in part by an increase in de novo lipogenesis that results from increased sterol element binding protein 1 (SREBP-1) activity. The nuclear receptor liver receptor homolog 1 (LRH-1) is an important regulator of intermediary metabolism in the liver, but its role in regulating lipogenesis is not well understood. Here, we have assessed the contribution of LRH-1 SUMOylation to the development of nonalcoholic fatty liver disease (NAFLD). Mice expressing a SUMOylation-defective mutant of LRH-1 (LRH-1 K289R mice) developed NAFLD and early signs of nonalcoholic steatohepatitis (NASH) when challenged with a lipogenic, high-fat, high-sucrose diet...
February 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27663419/inhibiting-poly-adp-ribosylation-increases-fatty-acid-oxidation-and-protects-against-fatty-liver-disease
#14
Karim Gariani, Dongryeol Ryu, Keir J Menzies, Hyon-Seung Yi, Sokrates Stein, Hongbo Zhang, Alessia Perino, Vera Lemos, Elena Katsyuba, Pooja Jha, Sandrine Vijgen, Laura Rubbia-Brandt, Yong Kyung Kim, Jung Tae Kim, Koon Soon Kim, Minho Shong, Kristina Schoonjans, Johan Auwerx
BACKGROUND & AIMS: To date, no pharmacological therapy has been approved for non-alcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the therapeutic potential of poly ADP-ribose polymerase (PARP) inhibitors in mouse models of NAFLD. METHODS: As poly ADP-ribosylation (PARylation) of proteins by PARPs consumes nicotinamide adenine dinucleotide (NAD+ ), we hypothesized that overactivation of PARPs drives NAD+ depletion in NAFLD. Therefore, we assessed the effectiveness of PARP inhibition to replenish NAD+ and activate NAD+ -dependent sirtuins, hence improving hepatic fatty acid oxidation...
January 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/27298334/lrh-1-dependent-programming-of-mitochondrial-glutamine-processing-drives-liver-cancer
#15
Pan Xu, Maaike H Oosterveer, Sokrates Stein, Hadrien Demagny, Dongryeol Ryu, Norman Moullan, Xu Wang, Emine Can, Nicola Zamboni, Arnaud Comment, Johan Auwerx, Kristina Schoonjans
Various tumors develop addiction to glutamine to support uncontrolled cell proliferation. Here we identify the nuclear receptor liver receptor homolog 1 (LRH-1) as a key regulator in the process of hepatic tumorigenesis through the coordination of a noncanonical glutamine pathway that is reliant on the mitochondrial and cytosolic transaminases glutamate pyruvate transaminase 2 (GPT2) and glutamate oxaloacetate transaminase 1 (GOT1), which fuel anabolic metabolism. In particular, we show that gain and loss of function of hepatic LRH-1 modulate the expression and activity of mitochondrial glutaminase 2 (GLS2), the first and rate-limiting step of this pathway...
June 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/27127236/nad%C3%A2-%C2%BA-repletion-improves-mitochondrial-and-stem-cell-function-and-enhances-life-span-in-mice
#16
Hongbo Zhang, Dongryeol Ryu, Yibo Wu, Karim Gariani, Xu Wang, Peiling Luan, Davide D'Amico, Eduardo R Ropelle, Matthias P Lutolf, Ruedi Aebersold, Kristina Schoonjans, Keir J Menzies, Johan Auwerx
Adult stem cells (SCs) are essential for tissue maintenance and regeneration yet are susceptible to senescence during aging. We demonstrate the importance of the amount of the oxidized form of cellular nicotinamide adenine dinucleotide (NAD(+)) and its effect on mitochondrial activity as a pivotal switch to modulate muscle SC (MuSC) senescence. Treatment with the NAD(+) precursor nicotinamide riboside (NR) induced the mitochondrial unfolded protein response and synthesis of prohibitin proteins, and this rejuvenated MuSCs in aged mice...
June 17, 2016: Science
https://www.readbyqxmd.com/read/26848619/bile-acid-fxr%C3%AE-pathways-regulate-male-sexual-maturation-in-mice
#17
Marine Baptissart, Emmanuelle Martinot, Aurélie Vega, Lauriane Sédes, Betty Rouaisnel, Angélique de Haze, Silvère Baron, Kristina Schoonjans, Françoise Caira, David H Volle
The bile acid receptor Farnesol-X-Receptor alpha (FRXα) is a member of the nuclear receptor superfamily. FRXα is expressed in the interstitial compartment of the adult testes, which contain the Leydig cells. In adult, short term treatment (12 hours) with FRXα agonist inhibits the expression of steroidogenic genes via the induction of the Small heterodimer partner (SHP). However the consequences of FRXα activation on testicular pathophysiology have never been evaluated. We demonstrate here that mice fed a diet supplemented with bile acid during pubertal age show increased incidence of infertility...
April 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/26541439/tgr5-and-immunometabolism-insights-from-physiology-and-pharmacology
#18
REVIEW
Alessia Perino, Kristina Schoonjans
In the past decade substantial progress has been made in understanding how the insurgence of chronic low-grade inflammation influences the physiology of several metabolic diseases. Tissue-resident immune cells have been identified as central players in these processes, linking inflammation to metabolism. The bile acid-responsive G-protein-coupled receptor TGR5 is expressed in monocytes and macrophages, and its activation mediates potent anti-inflammatory effects. Herein, we summarize recent advances in TGR5 research, focusing on the downstream effector pathways that are modulated by TGR5 activators, and on its therapeutic potential in inflammatory and metabolic diseases...
December 2015: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/26404765/eliciting-the-mitochondrial-unfolded-protein-response-by-nicotinamide-adenine-dinucleotide-repletion-reverses-fatty-liver-disease-in-mice
#19
Karim Gariani, Keir J Menzies, Dongryeol Ryu, Casey J Wegner, Xu Wang, Eduardo R Ropelle, Norman Moullan, Hongbo Zhang, Alessia Perino, Vera Lemos, Bohkyung Kim, Young-Ki Park, Alessandra Piersigilli, Tho X Pham, Yue Yang, Chai Siah Ku, Sung I Koo, Anna Fomitchova, Carlos Cantó, Kristina Schoonjans, Anthony A Sauve, Ji-Young Lee, Johan Auwerx
UNLABELLED: With no approved pharmacological treatment, nonalcoholic fatty liver disease (NAFLD) is now the most common cause of chronic liver disease in Western countries and its worldwide prevalence continues to increase along with the growing obesity epidemic. Here, we show that a high-fat high-sucrose (HFHS) diet, eliciting chronic hepatosteatosis resembling human fatty liver, lowers hepatic nicotinamide adenine dinucleotide (NAD(+) ) levels driving reductions in hepatic mitochondrial content, function, and adenosine triphosphate (ATP) levels, in conjunction with robust increases in hepatic weight, lipid content, and peroxidation in C57BL/6J mice...
April 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/26280129/bile-acids-trigger-glp-1-release-predominantly-by-accessing-basolaterally-located-g-protein-coupled-bile-acid-receptors
#20
Cheryl A Brighton, Juraj Rievaj, Rune E Kuhre, Leslie L Glass, Kristina Schoonjans, Jens J Holst, Fiona M Gribble, Frank Reimann
Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear farnesoid receptor and the apical sodium-coupled bile acid transporter ASBT. The aim of this study was to identify pathways important for GLP-1 release and to determine whether bile acids target their receptors on GLP-1-secreting L-cells from the apical or basolateral compartment...
November 2015: Endocrinology
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