A5027017283- Immune Cell Function and Interaction
- Pancreatic function and diabetes
- Diet, Metabolism, and Disease
- Metabolism, Diabetes, and Cancer
- Cannabis and Cannabinoid Research
- T-cell and B-cell Immunology
- Liver Disease Diagnosis and Treatment
- NF-κB Signaling Pathways
- Cytokine Signaling Pathways and Interactions
- Regulation of Appetite and Obesity
- Adipokines, Inflammation, and Metabolic Diseases
- Immunotherapy and Immune Responses
- Natural Antidiabetic Agents Studies
- Alzheimer's disease research and treatments
- interferon and immune responses
- Growth Hormone and Insulin-like Growth Factors
- Alcohol Consumption and Health Effects
- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Tryptophan and brain disorders
- Cell death mechanisms and regulation
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis C virus research
- Pharmacological Effects of Natural Compounds
- Cancer, Hypoxia, and Metabolism
Universidad de Málaga
2015-2024
Instituto de Investigación Biomédica de Málaga
2012-2023
Hospital Regional Universitario de Málaga
2007-2023
Instituto de Salud Carlos III
2015-2016
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition
2015-2016
Universidad de Navarra
2002-2004
Inserm
1992-2001
Consejo Superior de Investigaciones Científicas
1996-1998
Centro Nacional de Biotecnología
1994-1997
Universidad Autónoma de Madrid
1993-1996
We have identified a novel human gene of the Ig superfamily, designated LAG-3. Expression this is undetectable in resting PBL, while it found (a 2-kb message) activated T and NK cells. The LAG-3 includes eight exons; corresponding cDNA encodes 498-amino acid membrane protein with four extracellular IgSF domains. first one belongs to V-SET; particular since an extra loop middle domain unusual intrachain disulphide bridge. three other domains belong C2-SET. Strong internal homologies are...
The lymphocyte activation gene 3 (LAG-3), expressed in human activated T and natural killer (NK) cells, is closely related to CD4 at the protein levels. We report here initial characterization of LAG-3-encoded protein. have generated two monoclonal antibodies after immunization mice with a 30-amino acid peptide that corresponds an exposed extra loop region present LAG-3 immunoglobulin-like first domain. reactivity these reagents directed against since they recognize both membrane-expressed...
The treatment for cocaine use constitutes a clinical challenge because of the lack appropriate therapies and high rate relapse. Recent evidence indicates that immune system might be involved in pathogenesis addiction its co-morbid psychiatric disorders. This work examined plasma pro-inflammatory cytokine chemokine profile abstinent users (n = 82) who sought outpatient age/sex/body mass-matched controls 65). Participants were assessed with diagnostic interview Psychiatric Research Interview...
ABSTRACT Patients infected with hepatitis C virus (HCV) have an impaired response against HCV antigens while keeping immune competence for other antigens. We hypothesized that expression of proteins in dendritic cells (DC) might impair their antigen-presenting function, leading to a defective anti-HCV T-cell immunity. To test this hypothesis, DC from normal donors were transduced adenovirus coding core and E1 these (DC-CE1) used stimulate T lymphocytes. DC-CE1 poor stimulators allogeneic...
The endogenous cannabinoid acylethanolamide AEA (arachidonoylethanolamide; also known as anandamide) participates in the neuroadaptations associated with chronic ethanol exposure. However, no studies have described acute actions of on production and degradation. In present study, we investigated time course effects intraperitoneal administration (4 g/kg body mass) levels central peripheral tissues. Acute decreased cerebellum, hippocampus nucleus accumbens ventral striatum, well plasma...
Oleoylethanolamide (OEA) is a satiety factor that controls motivational responses to dietary fat. Here we show alcohol administration causes the release of OEA in rodents, which turn reduces consumption by engaging peroxisome proliferator-activated receptor-alpha (PPAR-α). This effect appears rely on peripheral signaling mechanisms as self-administration unaltered intracerebral PPAR-α agonist administration, and lesion sensory afferent fibers (by capsaicin) abrogates systemically...
Summary β-adrenergic receptor activation promotes brown adipose tissue (BAT) β-oxidation and thermogenesis by burning fatty acids during uncoupling respiration. Oleoylethanolamide (OEA) can inhibit feeding stimulate lipolysis activating the peroxisome proliferator-activating receptor-α (PPARα) in white (WAT). Here we explore whether PPARα potentiates effect of β3-adrenergic stimulation on energy balance mediated respective agonists OEA CL316243. The this pharmacological association was...
Interleukin-6 (IL-6) has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration IL-6 been reported to confer protection against steatosis, but plasma and tissue concentrations are elevated chronic liver diseases, including diseases associated obesity alcoholic ingestion. In this study, we further investigated role on steatosis induced through a high-fat diet (HFD) wild-type (WT) IL-6-deficient (IL-6(-/-)) mice. Additionally, HFD-fed...
Peptidic agonists of the glucagon-like peptide-1 receptor (GLP-1R) have gained a prominent role in therapy type-2 diabetes and are being considered for reducing food intake obesity. Potential advantages small molecules acting as positive allosteric modulators (PAMs) GLP-1R, including oral administration reduced unwanted effects, could improve utility this class drugs. Here, we describe discovery compound 9...
The amyloid cascade hypothesis is widely accepted as an explanation for the neuropathological changes in Alzheimer's disease (AD). However, role of amyloid-beta (Aβ) sole cause these being questioned. Using 5xFAD mouse model AD, we investigated various factors contributing to neuropathology, including genetic load (heterozygous (HTZ) versus homozygous (HZ) condition), behavioural phenotype, neuropathology markers, metabolic physiology, and gut microbiota composition at early (5 months age)...
The pro-B Ba/F3 cell line requires interleukin-3 and serum for growth, their removal results in apoptosis. cells transfected with the GH receptor (GHR) cDNA become able to proliferate response GH. To investigate role of control apoptosis, expressing either wild-type rat GHR (Ba/F3 GHR) or a mutated ILV/T) were used. We show that cells, but not parental ILV/T survive absence growth factor. Furthermore, an autocrine/paracrine mode action was suggested by demonstration produce GH, addition...
Dependence of murine pro-B Ba/F3 cells on interleukin-3 can be substituted by GH when are stably transfected with the receptor (GHR) complementary DNA. Recently, we demonstrated that produce GH, which is responsible for survival expressing GHR. This effect involves activation nuclear factor-κB (NF-κB). Here, examined signaling pathways mediating proliferation growth factor-deprived GHR cells. Exogenous stimulation induced cyclins E and A cyclin-dependent kinase inhibitor p21waf1/cip1...
Superantigens have multiple pleiotropic effects in vivo, causing the activation, proliferation, and deletion of specific T cells. In our study, we analyzed bacterial superantigen Staphylococcus aureus enterotoxin B (SEB) on peripheral cells vivo. As an internal control took advantage a IgG2a mAb, F23.1 (anti-V beta 8), that recognizes products from same V gene family as recognized by SEB. Suprisingly, not only SEB, but also primes to undergo oligonucleosomal DNA fragmentation typical for...
Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of in expression glucose/pyruvate/tricarboxylic acid (TCA) metabolism rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) α-ketoacid complexes with diaphorase activity mitochondria, was specifically analyzed. After assessing effectiveness receptor antagonist AM251 (3 mg kg-1, 14 days) on food intake and body weight, could identified seven key enzymes from...
High-fat diet-induced obesity (DIO) is associated with fatty liver and elevated IL-6 circulating levels. administration in rodents has yielded contradictory results regarding its effects on steatosis progression. In some models of disease, high doses human ameliorate the steatosis, whereas restoration DIO IL-6-/- mice up-regulates hepatic lipogenic enzymes aggravates steatosis. We further examined chronic low murine lipid metabolism WT DIO. was delivered twice daily C57BL/6J for 15 days. The...
Glucokinase is essential for glucose-stimulated insulin release from the pancreatic beta-cell, serving as glucose sensor in humans. Inactivating or activating mutations of glucokinase lead to different forms disease, i.e. GCK-monogenic diabetes youth, permanent neonatal (inactivating mutations), and congenital hyperinsulinism, respectively. Here we present a novel gene (GCK)-activating mutation (p.E442K) found an infant with hypoglycemia (1.5 mmol/liter) two other family members suffering...
To characterize the metabolic actions of D-Pinitol, a dietary inositol, in male Wistar rats, we analyzed its oral pharmacokinetics and effects on (a) secretion hormones regulating metabolism (insulin, glucagon, IGF-1, ghrelin, leptin adiponectin), (b) insulin signaling liver (c) expression glycolytic neoglucogenesis enzymes. Oral D-Pinitol administration (100 or 500 mg/Kg) resulted rapid absorption distribution to plasma compartments. Its reduced insulinemia HOMA-IR, while maintaining...
Obesity is currently a major epidemic in the developed world. However, we lack wide range of effective pharmacological treatments and therapies against obesity, those approved are not devoid adverse effects. Dietary components such as palmitoleic acid have been proposed to improve metabolic disbalance although mechanisms involved well understood. Both (POA) oleic (OA) can be transformed N-acylethanolamines (NAEs), mediating effects dietary POA OA. To test this hypothesis, here, study on food...
Recent evidence links brain insulin resistance with neurodegenerative diseases, where hyperphosphorylated tau protein contributes to neuronal cell death. In the present study, we aimed evaluate if d-pinitol inositol, which acts as an sensitizer, affects phosphorylation status of protein.We studied pharmacological effect on signalling and in hippocampus Wistar Zucker rats. To this end, evaluated by western blotting Akt pathway its downstream proteins being one main insulin-mediator pathways....
Acylethanolamides (NAEs) are bioactive lipids derived from diet fatty acids that modulate important homeostatic functions, including appetite, acid synthesis, mitochondrial respiration, inflammation, and nociception. Among the naturally circulating NAEs, pharmacology of those either arachidonic (Anandamide), oleic (OEA), palmitic (PEA) have been extensively characterized in diet-induced obesity. For present work, we extended studies to linoleoylethanolamide (LEA), one most abundant NAEs...