- Adipose Tissue and Metabolism
- Diet and metabolism studies
- Pancreatic function and diabetes
- Dietary Effects on Health
- Cellular transport and secretion
- Liver Disease Diagnosis and Treatment
- Sirtuins and Resveratrol in Medicine
- Adipokines, Inflammation, and Metabolic Diseases
- Autophagy in Disease and Therapy
- Metabolism, Diabetes, and Cancer
- Peroxisome Proliferator-Activated Receptors
- Diet, Metabolism, and Disease
- Regulation of Appetite and Obesity
- Genomics, phytochemicals, and oxidative stress
- Endoplasmic Reticulum Stress and Disease
- Cancer, Lipids, and Metabolism
- Genetics, Aging, and Longevity in Model Organisms
- Circadian rhythm and melatonin
- Lipid Membrane Structure and Behavior
- Lipid metabolism and disorders
- Lipid metabolism and biosynthesis
- Cancer, Hypoxia, and Metabolism
- Gut microbiota and health
- Mitochondrial Function and Pathology
- Biochemical effects in animals
IMDEA Food
2018-2024
Madrid Institute for Advanced Studies
2018-2024
Universidad Autónoma de Madrid
2018-2024
Centro de Investigación Biomédica en Red
2011-2024
National Institutes of Health
2015-2023
National Institute on Aging
2015-2023
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition
2012-2023
University of Córdoba
2009-2020
Instituto de Salud Carlos III
2011-2020
Instituto Maimónides de Investigación Biomédica de Córdoba
2011-2020
Summary Mitochondrial function in human skeletal muscle declines with age. Most evidence for this decline comes from studies that assessed mitochondrial indirectly, and the impact of such deterioration respect to physical has not been clearly delineated. We hypothesized respiration permeabilized fibers age correlates phosphocreatine postexercise recovery rate ( kPC r), performance, aerobic fitness. was by high‐resolution respirometry saponin‐permeabilized vastus lateralis biopsies 38...
Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified small GTPase Rab18 as a component LD coat. However, specific contribution to adipocyte function remains be elucidated. Herein, we analyzed expression, intracellular localization relation metabolic status We show production increases during adipogenic...
While therapeutic modulation of miRNAs provides a promising approach for numerous diseases, the promiscuous nature raises concern over detrimental off-target effects. miR-33 has emerged as likely target treatment cardiovascular diseases. However, deleterious effects long-term anti-miR-33 therapies and predisposition miR-33−/− mice to obesity metabolic dysfunction exemplify possible pitfalls miRNA-based therapies. Our work an in-depth characterization explores mechanisms by which loss...
Early onset Parkinson's disease is caused by variants in PINK1, parkin, and DJ-1. PINK1 parkin operate pathways that preserve mitochondrial integrity, but the function of DJ-1 how it relates to poorly understood. A series unbiased high-content screens were used analyze changes at protein, RNA, metabolite level rodent brains lacking Results validated using targeted approaches, cellular assays performed probe mechanisms involved. We find both rat mouse brains, knockout results an age-dependent...
Patients with nonalcoholic fatty liver disease (NAFLD) are reported to have low growth hormone (GH) production and/or hepatic GH resistance. replacement can resolve the condition in diet-induced obese rodents and GH-deficient patients. However, it remains be determined whether this inhibitory action of is due direct regulation lipid metabolism. Therefore, an adult-onset, hepatocyte-specific, receptor (GHR) knockdown (aLivGHRkd) mouse was developed model resistance humans that may occur after...
Abstract Cancer incidence increases with age and is a leading cause of death. Caloric restriction (CR) confers benefits on health survival delays cancer. However, due to CR’s stringency, dietary alternatives offering the same cancer protection have become increasingly attractive. Short cycles plant-based diet designed mimic fasting (FMD) are protective against tumorigenesis without chronic calories. Yet, it unclear whether time, level restriction, or nutrient composition primary driver...
Cytochrome b5 reductases (CYB5R) are required for the elongation and desaturation of fatty acids, cholesterol synthesis mono-oxygenation cytochrome P450 enzymes, all which associated with protection against metabolic disorders. However, physiological role CYB5R in context metabolism, healthspan aging remains ill-defined. We generated CYB5R-overexpressing flies (CYB5R-OE) created a transgenic mouse line overexpressing CYB5R3 (CYB5R3-Tg) C57BL/6J background to investigate function this class...
Background & AimsNonalcoholic steatohepatitis (NASH) is commonly observed in patients with type 2 diabetes, and thiazolidinediones (TZD) are considered a potential therapy for NASH. Although TZD increase insulin sensitivity partially reduce steatosis alanine aminotransferase, the efficacy of on resolving liver pathology limited. In fact, may activate peroxisome proliferator-activated receptor gamma (PPARγ) hepatocytes promote steatosis. Therefore, we assessed role that hepatocyte-specific...
Adiponectin binds to two widely expressed receptors (AdipoR1 and AdipoR2) that contain seven transmembrane domains but, unlike G-protein coupled receptors, present an extracellular C terminus a cytosolic N terminus. Recently, AdipoR1 was found associate in high order complexes. However, it is still unknown whether AdipoR2 may also form homomers or heteromers with if such interactions be functionally relevant. Herein, we have analyzed the oligomerization pattern of AdipoRs by FRET...
Aims: Obesity is characterized by a low-grade systemic inflammatory state and adipose tissue (AT) dysfunction, which predispose individuals to the development of insulin resistance (IR) metabolic disease. However, subset obese individuals, referred as metabolically healthy (MHO) are protected from obesity-associated abnormalities. Here, we aim at identifying molecular factors pathways in adipocytes that responsible for progression insulin-sensitive insulin-resistant, unhealthy (MUHO)...
Ghrelin, a stomach-derived peptide, stimulates feeding behavior and adiposity. For its orexigenic action, ghrelin triggers central SIRT1/p53/AMPK pathway. The tumor suppressor p53 also plays an important role in white adipose tissue (WAT), where it is up-regulated the adipocytes of obese mice. It not known, however, whether has any mediating peripheral action ghrelin. In present study, chronic treatment resulted increased body weight fat-mass gain wild-type Correspondingly, mRNA levels...
Glucagon-like peptide-1 (GLP-1) analogues improve glycaemic control in type 2 diabetic (T2D) patients and cause weight loss obese subjects by as yet unknown mechanisms. We recently demonstrated that the GLP-1 receptor, which is present adipocytes stromal vascular fraction of human adipose tissue (AT), up-regulated AT insulin-resistant morbidly compared with healthy lean subjects. The aim this study was to explore effects vitro vivo administration its on adipocyte functions from T2D
Summary Calorie restriction ( CR ) is one of the most robust means to improve health and survival in model organisms. imposes a metabolic program that leads increased stress resistance delayed onset chronic diseases, including cancer. In rodents, induces upregulation two NADH ‐dehydrogenases, namely NAD (P)H:quinone oxidoreductase 1 Nqo1 cytochrome b 5 reductase 3 Cyb5r3 ), which provide electrons for energy metabolism. It has been proposed this may be responsible some beneficial effects ,...
Adipose tissue dysregulation in obesity strongly influences systemic metabolic homeostasis and is often linked to insulin resistance (IR). However, the molecular mechanisms underlying adipose dysfunction are not fully understood. Herein, a proteomic analysis of subcutaneous (SC) omental (OM) fat from lean subjects obese individuals with different degrees sensitivity was performed identify biomarkers related obesity-associated disease. Our results suggest that both extracellular matrix (ECM)...
Abstract Fasting exerts beneficial effects in mice and humans, including protection from chemotherapy toxicity. To explore the involved mechanisms, we collect blood humans before after 36 or 24 hours of fasting, respectively, measure lipid composition erythrocyte membranes, circulating micro RNAs (miRNAs), RNA expression at peripheral mononuclear cells (PBMCs). coordinately affects proportion polyunsaturated versus saturated monounsaturated fatty acids membrane; reduces insulin...
Abstract Thiazolidinediones (TZD) are peroxisome proliferator-activated receptor γ (PPARγ) agonists that may reduce hepatic steatosis through their effects in adipose tissue and therefore have been assessed as potential therapies to treat nonalcoholic fatty liver disease (NAFLD) humans. However, some studies suggest expression activation of hepatocyte PPARγ promotes would limit the benefits TZD a NAFLD therapy. To further explore this possibility, we examined impact short-term rosiglitazone...
Abstract Dietary restriction has shown benefits in physiological, metabolic, and molecular signatures associated with aging but is a difficult lifestyle to maintain for most individuals. In mice, less restrictive diet that allows cyclical periods of reduced calories mitigates phenotypes, yet the effects such an intervention genetically heterogenous, higher-order mammal not been examined. Here, using middle-aged rhesus macaques matched age sex, we show regimen 4 days low-calorie intake...
Abstract Chronic nutrient excess leads to metabolic disorders and insulin resistance. Activation of stress-responsive pathways via Nrf2 activation contributes energy metabolism regulation. Here, inducible in mice transgenesis the target, NQO1, conferred protection from diet-induced defects through preservation glucose homeostasis, sensitivity, lipid handling with improved physiological outcomes. NQO1-RNA interaction mediated association inhibition translational machinery skeletal muscle NQO1...