A5088941969- Adipose Tissue and Metabolism
- Adipokines, Inflammation, and Metabolic Diseases
- Melanoma and MAPK Pathways
- Cardiac Fibrosis and Remodeling
- Pancreatic function and diabetes
- Immune Cell Function and Interaction
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Tryptophan and brain disorders
- RNA modifications and cancer
- Muscle Physiology and Disorders
- Circadian rhythm and melatonin
- Liver Disease Diagnosis and Treatment
- Protein Kinase Regulation and GTPase Signaling
- Epigenetics and DNA Methylation
- Receptor Mechanisms and Signaling
- Fibroblast Growth Factor Research
- Peroxisome Proliferator-Activated Receptors
- Signaling Pathways in Disease
- Lipid metabolism and biosynthesis
- Kruppel-like factors research
- GDF15 and Related Biomarkers
- Pancreatic and Hepatic Oncology Research
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Cancer-related Molecular Pathways
Spanish National Centre for Cardiovascular Research
2016-2025
Spanish National Cancer Research Centre
2024-2025
Centro Nacional de Epidemiología
2024
Centro de Investigación del Cáncer
2024
University of Pittsburgh
2008-2009
Hepatocellular carcinoma (HCC) is the sixth most common cancer type and fourth leading cause of cancer-related death. This appears with higher incidence in men during obesity; however, specific mechanisms underlying this correlation are unknown. Adipose tissue, a key organ metabolic syndrome, shows evident gender disparities production adipokines. Levels important adipokine adiponectin decrease puberty, as well obese state. Here, we show that levels responsible for increased liver risk...
Increasing the thermogenic capacity of adipose tissue to enhance organismal energy expenditure is considered a promising therapeutic strategy combat obesity. Here, we report that expression p38 MAPK activator MKK6 elevated in white obese individuals. Using knockout animals and shRNA, show Mkk6 deletion increases tissue, protecting mice against diet-induced obesity development diabetes. Deletion T3-stimulated UCP1 adipocytes, thereby increasing their capacity. Mechanistically, demonstrate...
Significance Obesity is associated with hepatic steatosis and activation of the cJun NH 2 -terminal kinase (JNK) stress-signaling pathway. Studies in mice demonstrate that JNK deficiency liver prevents development steatosis. This observation suggests inhibition signaling may represent a possible treatment for However, long-term consequences are poorly understood. Here we loss causes changes cholesterol bile acid metabolism promote cholestasis, duct proliferation, intrahepatic...
Liver metabolism follows diurnal fluctuations through the modulation of molecular clock genes. Disruption this can result in metabolic disease but its potential regulation by immune cells remains unexplored. Here, we demonstrated that steady state, neutrophils infiltrated mouse liver following a circadian pattern and regulated hepatocyte clock-genes neutrophil elastase (NE) secretion. NE signals c-Jun NH2-terminal kinase (JNK) inhibiting fibroblast growth factor 21 (FGF21) activating Bmal1...
Obesity poses a global health challenge, demanding deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role mitochondrial protein Methylation-controlled J (MCJ/DnaJC15) in orchestrating brown (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident human mouse samples. MCJKO mice, even without UCP1, fundamental thermogenic protein, exhibit elevated BAT Electron microscopy unveils changes morphology resembling activation....
Adipose tissue has emerged as an important regulator of whole-body metabolism, and its capacity to dissipate energy in the form heat acquired a special relevance recent years potential treatment for obesity. In this context, p38MAPK pathway arisen key player thermogenic program because it is required activation brown adipose (BAT) thermogenesis participates also transformation white (WAT) into BAT-like depot called beige/brite tissue. Here, using mice that are deficient p38α specifically...
Abstract The metabolic functions of the liver are spatially organized in a phenomenon called zonation, linked to differential exposure portal and central hepatocytes nutrient-rich blood. mTORC1 signaling pathway controls cellular metabolism response nutrients insulin fluctuations. Here we show that simultaneous genetic activation nutrient hormone results impaired establishment postnatal zonal identity hepatocytes. Mutant fail upregulate postnatally expression Frizzled receptors 1 8, reduced...
Stress-activated p38 kinases control a plethora of functions, and their dysregulation has been linked to the development steatosis, obesity, immune disorders, cancer. Therefore, they have identified as potential targets for novel therapeutic strategies. There are four family members (p38α, p38β, p38γ, p38δ) that activated by MKK3 MKK6. Here, we demonstrate lack MKK6 reduces lifespan in mice. Longitudinal study cardiac function KO mice showed young develop hypertrophy which progresses...
The production of phosphatidic acid plays a crucial role in the activation ERK cascade. This was linked to binding phosphatidate specific polybasic site within kinase domain Raf-1. Here we show that promotes phosphorylation intact cells but does not activate Raf vitro. suppressor Ras (KSR) contains sequence homologous Direct synthetic peptides derived from sequences domains Raf-1 and KSR demonstrated by spectroscopic techniques. specificity these interactions confirmed using lipids mutated...
The fluorescent properties of the amino acid tryptophan make it a useful tool for fluorometric assays. Because fluorescence is remarkably sensitive to polarity environment, can be used determine affinity tryptophan-containing peptides phospholipid vesicles varying compositions. Here, we describe method using binding affinities derived from proteins Raf-1 and KSR-1 small unilamellar containing phosphatidic acid. extrapolated measure other or lipid vesicles.
Obesity features excessive fat accumulation in several body tissues and induces a state of chronic low-grade inflammation that contributes to the development diabetes, steatosis, insulin resistance. Recent research has shown this is crucially dependent on p38 pathway activity macrophages, suggesting inhibition as possible treatment for obesity comorbidities. Nevertheless, we report here lack activation myeloid cells worsens high-fat diet-induced obesity, steatosis. Deficient increases...
During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This change is contemporaneous up-regulation and activation p38γ p38δ stress-activated protein kinases in heart. We demonstrate that p38γ/δ contribute early cardiac switch through inhibitory phosphorylation glycogen synthase 1 (GYS1) metabolism inactivation. Premature induction newborn mice results an GYS1 inhibition...
Skeletal muscle has gained recognition as an endocrine organ releasing myokines upon contraction during physical exercise. These exert both local and pleiotropic health benefits, underscoring the crucial role of function in countering obesity contributing to overall positive effects exercise on health. Here, we found that activates p38γ, increasing locomotor activity through secretion interleukin-15 (IL-15). IL-15 signals motor cortex, stimulating activity. This activation leading increase...
Skeletal muscle, with its remarkable plasticity and dynamic adaptation, serves as a cornerstone of locomotion metabolic homeostasis in the human body. Muscle tissue, extraordinary capacity for force generation energy expenditure, plays fundamental role movement, metabolism, overall health. In this context, we sought to determine p38α mitochondrial metabolism since dynamics play crucial development muscle-related diseases that result muscle weakness.
Abstract Obesity is characterized with low grade inflammation, energy imbalance and impaired thermogenesis. The role of regulatory T cells (Treg) in inflammation-mediated maladaptive thermogenesis has not been well established. We discovered that p38 pathway a key regulator cell-mediated adipose tissue (AT) inflammation browning. Mice specific deletion the activators, MKK3/6, were protected against diet-induced obesity AT improving their metabolic profile, higher browning identified IL-35 as...
ABSTRACT cJun NH 2 -terminal kinase (JNK) inhibition has been suggested as a potential treatment for insulin resistance and steatosis through activation of the transcription factor PPARα. However, long-term consequences have not evaluated. We found that hepatic JNK deficiency alters bile acid cholesterol metabolism, resulting in expression FGF15 ERK cholangiocytes, which ultimately promotes their proliferation. Genetic inactivation PPARα identifies hyperactivation molecular mechanism these...