A5077630402- Liver Disease Diagnosis and Treatment
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Diet, Metabolism, and Disease
- Peroxisome Proliferator-Activated Receptors
- Folate and B Vitamins Research
- Lipid metabolism and biosynthesis
- Diet and metabolism studies
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Endoplasmic Reticulum Stress and Disease
- ATP Synthase and ATPases Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Protein Degradation and Inhibitors
- Liver physiology and pathology
- Metabolism, Diabetes, and Cancer
- Metabolomics and Mass Spectrometry Studies
- Alcohol Consumption and Health Effects
- Bone and Dental Protein Studies
- Fibroblast Growth Factor Research
- Liver Disease and Transplantation
- Diabetes and associated disorders
- Drug Transport and Resistance Mechanisms
University of the Basque Country
2013-2024
BioCruces Health research Institute
2014-2023
Hospital de Cruces
2020-2023
Marqués de Valdecilla University Hospital
2017
Instituto de Investigación Marqués de Valdecilla
2017
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2017
Centro de Investigación Biomédica en Red
2017
Fatty acid translocase CD36 (FAT/CD36) mediates uptake and intracellular transport of long-chain fatty acids in diverse cell types. While the pathogenic role FAT/CD36 hepatic steatosis rodents is well-defined, little known about its significance human liver diseases.To examine expression cellular subcellular distribution within patients with non-alcoholic disease (NAFLD) chronic hepatitis C virus (HCV) infection.34 (NAS), 30 steatohepatitis (NASH), 66 HCV genotype 1 (HCV G1) 32 non-diseased...
Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis liver and lipid oxidation brown adipose tissue (BAT) through parasympathetic (PSNS) sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic with parallel stimulation of thermogenic program BAT. The action depends on AMP-activated protein kinase (AMPK)-induced regulation two signaling pathways ventromedial nucleus hypothalamus (VMH):...
Methionine adenosyltransferase 1A ( MAT1A ) and glycine N -methyltransferase GNMT are the primary genes involved in hepatic S-adenosylmethionine (SAMe) synthesis degradation, respectively. Mat1a ablation mice induces a decrease SAMe, activation of lipogenesis, inhibition triglyceride (TG) release, steatosis. Gnmt -deficient mice, despite showing large increase also develop We hypothesized that as an adaptive response to SAMe accumulation, phosphatidylcholine (PC) by way...
Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease (NAFLD) which sets stage for further damage. The mechanism progression NASH involves multiple parallel hits including oxidative stress, mitochondrial dysfunction, inflammation and others. Manipulation any these pathways may be an approach to prevent development progression. Aramchol (arachidyl-amido cholanoic acid) presently in a phase IIb study. aim this study was investigate Aramchol's action its...
Abstract Very low-density lipoprotein (VLDL) secretion provides a mechanism to export triglycerides (TG) from the liver peripheral tissues, maintaining lipid homeostasis. In nonalcoholic fatty disease (NAFLD), VLDL disturbances are unclear. Methionine adenosyltransferase (MAT) is responsible for S -adenosylmethionine (SAMe) synthesis and MAT I III products of MAT1A gene. Deficient activities SAMe content in have been associated with NAFLD, but whether required normal assembly remains...
// Lucía Barbier-Torres 1 , Teresa C. Delgado Juan L. García-Rodríguez Imanol Zubiete-Franco David Fernández-Ramos Xabier Buqué 2 Ainara Cano 3 Virginia Gutiérrez-de Itziar Fernández-Domínguez Fernando Lopitz-Otsoa Pablo Fernández-Tussy Loreto Boix 4,5 Jordi Bruix Erica Villa 6 Azucena Castro Shelly Lu 7 Patricia Aspichueta Dimitris Xirodimas 8 Marta Varela-Rey José M. Mato Naiara Beraza and María...
Hyperhomocysteinemia (HHcy) causes increased oxidative stress and is an independent risk factor for cardiovascular disease. Oxidative now believed to be a major contributory in the development of non alcoholic fatty liver disease, most common disorder worldwide. In this study, changes which occur homocysteine (Hcy) metabolism high fat-diet induced disease (NAFLD) rats were investigated. After feeding standard low fat diet (control) or (57% metabolisable energy as fat) 18 weeks, concentration...
Background and Aims G protein–coupled receptor (GPR) 55 is a putative cannabinoid receptor, l‐α‐lysophosphatidylinositol (LPI) its only known endogenous ligand. Although GPR55 has been linked to energy homeostasis in different organs, specific role lipid metabolism the liver contribution pathophysiology of nonalcoholic fatty disease (NAFLD) remains unknown. Approach Results We measured (1) expression patients with NAFLD compared individuals without obesity disease, as well animal models...
Lipid metabolism rearrangements in nonalcoholic fatty liver disease (NAFLD) contribute to progression. NAFLD has emerged as a major risk for hepatocellular carcinoma (HCC), where metabolic reprogramming is hallmark. Identification of drivers might reveal therapeutic targets improve HCC treatment. Here, we investigated the contribution transcription factors E2F1 and E2F2 NAFLD-related their involvement rewiring during In mice receiving high-fat diet (HFD) diethylnitrosamine (DEN)...
Altered methionine metabolism is associated with weight gain in obesity. The adenosyltransferase (MAT), catalyzing the first reaction of cycle, plays an important role regulating lipid metabolism. However, its obesity, when a plethora metabolic diseases occurs, still unknown. By using antisense oligonucleotides (ASO) and genetic depletion Mat1a, here, we demonstrate that Mat1a deficiency diet-induce obese or genetically mice prevented reversed obesity obesity-associated insulin resistance...
Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with dismal prognosis. We investigated if lipid metabolism is disrupted in CCA and its role tumor proliferation.The vitro vivo tumorigenic capacity five human cell lines was analyzed. Proteome, content, metabolic fluxes were evaluated cells compared normal cholangiocytes (NHC). The Akt1/NOTCH1 intracellular cytoplasmic domain (Nicd1)-driven mouse model also evaluated. proteome enriched pathways involved lipoprotein...
We aimed to characterize the primary abnormalities associated with fat accumulation and vulnerability hepatocellular injury of obesity-related fatty liver. performed functional analyses comparative transcriptomics isolated hepatocytes from livers obese insulin-resistant Zucker rats (comprising mild severe hepatic steatosis) age-matched lean littermates, searching for novel genes linked chronic steatosis. Of tested genome, 1.6% was identified as steatosis linked. Overexpressed were mainly...
Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver fibrosis, hepatocellular carcinoma, more recently, non-alcoholic fatty disease (NAFLD). Herein, we propose to address the effects of neddylation inhibition underlying mechanisms pre-clinical models NAFLD.Hepatic measured by immunohistochemical analysis NEDD8 serum levels ELISA assay were evaluated NAFLD clinical samples. The using pharmacological small...
Background & AimsVery-low-density lipoproteins (VLDLs) export lipids from the liver to peripheral tissues and are precursors of low-density-lipoproteins. Low levels hepatic S-adenosylmethionine (SAMe) decrease triglyceride (TG) secretion in VLDLs, contributing hepatosteatosis methionine adenosyltransferase 1A knockout mice but nothing is known about effect SAMe on circulating VLDL metabolism.We wanted investigate whether excess could disrupt plasma metabolism unravel mechanisms...
p53 family members control several metabolic and cellular functions. The ortholog p63 modulates adaptations to stress has a major role in cell maintenance proliferation. Here we show that regulates hepatic lipid metabolism. Mice with liver-specific deletion develop steatosis increased levels of p63. Down-regulation attenuates liver knockout mice diet-induced obese mice, whereas the activation induces accumulation. Hepatic overexpression N-terminal transactivation domain TAp63 through IKKβ...
Autophagy-related gene 3 (ATG3) is an enzyme mainly known for its actions in the LC3 lipidation process, which essential autophagy. Whether ATG3 plays a role lipid metabolism or contributes to non-alcoholic fatty liver disease (NAFLD) remains unknown.By performing proteomic analysis on livers from mice with genetic manipulation of hepatic p63, regulator acid metabolism, we identified as new target downstream p63. was evaluated samples patients NAFLD. Further, performed human hepatocyte cell...
In myocytes and adipocytes, insulin increases fatty acid translocase (FAT)/CD36 translocation to the plasma membrane (PM), enhancing (FA) uptake. Evidence links increased hepatic FAT/CD36 protein amount gene expression with hyperinsulinemia in animal models patients liver, but whether regulates expression, amount, distribution, function hepatocytes is currently unknown. To investigate this, content isolated hepatocytes, subfractions of organelles, density-gradient was analyzed obese lean...
Recent reports have implicated the p53 tumor suppressor in regulation of lipid metabolism. We hypothesized that pharmacological activation with low-dose doxorubicin, which is widely used to treat several types cancer, may beneficial effects on nonalcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH).We long-term by i.p. or oral administration doxorubicin different animal models NAFLD (high fat diet containing 45% 60% kcal fat) NASH (methionine- choline-deficient choline deficiency...
There has been an intense focus to uncover the molecular mechanisms by which fasting triggers adaptive cellular responses in major organs of body. Here, we show that mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor nutrition fine-tune catabolic-fasting response modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production liver, together with FGF21-mediated...
Susceptibility to develop nonalcoholic fatty liver disease (NAFLD) has genetic bases, but the associated variants are uncertain. The aim of present study was identify that could help prognose and further understand genetics development NAFLD. Allele frequencies 3,072 single-nucleotide polymorphisms (SNPs) in 92 genes were characterized 69 NAFLD patients 217 healthy individuals. markers showed significant allele-frequency differences pilot groups subsequently studied 451 304 controls. Besides...
Abstract Osteopontin (OPN), a senescence‐associated secretory phenotype factor, is increased in patients with nonalcoholic fatty liver disease (NAFLD). Cellular senescence has been associated age‐dependent hepatosteatosis. Thus, we investigated the role of OPN age‐related For this, human serum samples, animal models aging, and cell lines which was induced were used. Metabolic fluxes, lipid, protein concentration determined. Among individuals normal liver, observed positive correlation...
Osteopontin (OPN) is involved in different liver pathologies which metabolic dysregulation a hallmark. Here, we investigated whether OPN could alter liver, and more specifically hepatocyte, lipid metabolism the mechanism involved. In mice, lack of enhanced cholesterol 7α-hydroxylase (CYP7A1) levels promoted loss phosphatidylcholine (PC) content liver; vivo treatment with recombinant (r)OPN caused opposite effects. rOPN directly decreased CYP7A1 through activation focal adhesion kinase-AKT...
recent evidence suggests a causal link between serum uric acid and the metabolic syndrome, diabetes mellitus, arterial hypertension, renal cardiac disease. Uric is an endogenous danger signal activator of inflammasome, has been independently associated with increased risk cirrhosis.six hundred thirty-four patients from nation-wide HEPAMET registry biopsy-proven NAFLD (53% NASH) were analyzed to determine whether hyperuricemia related advanced liver damage in non-alcoholic fatty disease...
Abstract Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic worldwide. Liver biopsy remains gold standard for diagnosis and staging disease. There a clinical need noninvasive diagnostic tools risk stratification, follow‐up, monitoring treatment response that are currently lacking, as well preclinical models recapitulate etiology human condition. We have characterized progression NAFLD in eNOS −/− mice fed high fat diet (HFD) using Dixon‐based magnetic resonance imaging...