A5071491630- Regulation of Appetite and Obesity
- Adipose Tissue and Metabolism
- Pancreatic function and diabetes
- Biochemical Analysis and Sensing Techniques
- Mitochondrial Function and Pathology
- Sleep and Wakefulness Research
- Growth Hormone and Insulin-like Growth Factors
- Metabolism, Diabetes, and Cancer
- Diet and metabolism studies
- Lipid metabolism and disorders
- Adipokines, Inflammation, and Metabolic Diseases
- Circadian rhythm and melatonin
- Ion channel regulation and function
- Diabetes Treatment and Management
- Neuroinflammation and Neurodegeneration Mechanisms
- Congenital heart defects research
- Neuroendocrine regulation and behavior
- Bat Biology and Ecology Studies
- Erythrocyte Function and Pathophysiology
- Viral Infections and Vectors
- Mosquito-borne diseases and control
- Genetic Syndromes and Imprinting
- Cannabis and Cannabinoid Research
- Sphingolipid Metabolism and Signaling
- Fibroblast Growth Factor Research
Achucarro Basque Center for Neuroscience
2022-2025
Yale University
2015-2024
Ikerbasque
2022-2024
Medical University of Vienna
2024
Centro de Investigación en Red en Enfermedades Cardiovasculares
2023
Universidade de Santiago de Compostela
2008-2020
Center for Research in Molecular Medicine and Chronic Diseases
2017-2020
Instituto de Salud Carlos III
2009-2020
Fraternal Order of Eagles
2018
University of Iowa
2018
The mechanisms underlying Zika virus (ZIKV)-related microcephaly and other neurodevelopment defects remain poorly understood. Here, we describe the derivation characterization, including single-cell RNA-seq, of neocortical spinal cord neuroepithelial stem (NES) cells to model early human ZIKV-related neuropathogenesis. By analyzing NES cells, organotypic fetal brain slices, a ZIKV-infected micrencephalic brain, show that ZIKV infects both as well their homolog, radial glial (RGCs), causing...
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):...
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that operates as sensor cellular energy status and effector for its coupling to cell growth proliferation. At the hypothalamic arcuate nucleus, mTOR signaling has been recently proposed transducer leptin effects on homeostasis food intake. However, whether central also participates in metabolic regulation fertility remains unexplored. We provide herein evidence involvement control puberty onset LH secretion, likely via...
We investigated a possible role of the central glucagon-like peptide (GLP-1) receptor system as an essential brain circuit regulating adiposity through effects on nutrient partitioning and lipid metabolism independent from feeding behavior. Both lean diet-induced obesity mice were used for our experiments. GLP-1 (7–36) amide was infused in 2 or 7 d. The expression key enzymes involved measured by real-time PCR Western blot. To test hypothesis that sympathetic nervous may be responsible...
The success of antipsychotic drug treatment in patients with schizophrenia is limited by the propensity these drugs to induce hyperphagia, weight gain and other metabolic disturbances, particularly evident for olanzapine clozapine. However, molecular mechanisms involved antipsychotic-induced hyperphagia remain unclear. Here, we investigate effect administration on regulation hypothalamic controlling food intake, namely neuropeptide expression AMP-activated protein kinase (AMPK)...
Alterations in ectopic lipid deposition and circulating lipids are major risk factors for developing cardiometabolic diseases. Angiopoietin-like protein 4 (ANGPTL4), a that inhibits lipoprotein lipase (LPL), controls fatty acid (FA) uptake adipose oxidative tissues regulates triacylglycerol-rich (TAG-rich) lipoproteins. Unfortunately, global depletion of ANGPTL4 results severe metabolic abnormalities, inflammation, fibrosis when mice fed high-fat diet (HFD), limiting our understanding the...
Astrocytes represent central regulators of brain glucose metabolism and neuronal function. They have recently been shown to adapt their function in response alterations nutritional state through responding the energy state-sensing hormones leptin insulin. Here, we demonstrate that glucagon-like peptide (GLP)-1 inhibits uptake promotes β-oxidation cultured astrocytes. Conversely, postnatal GLP-1 receptor (GLP-1R) deletion glial fibrillary acidic protein (GFAP)-expressing astrocytes impairs...
Hyperthyroidism is characterized in rats by increased energy expenditure and marked hyperphagia. Alterations of thermogenesis linked to hyperthyroidism are associated with dysregulation hypothalamic AMPK fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear. Here, we demonstrate that hyperthyroid exhibit up-regulation mammalian target rapamycin (mTOR) signalling pathway mRNA levels agouti-related protein (AgRP)...
Brown adipose tissue (BAT) controls triglyceride-rich lipoprotein (TRL) catabolism. This process is mediated by the lipase (LPL), an enzyme that catalyzed hydrolysis of triglyceride (TAG) in glycerol and fatty acids (FA), which are burned to generate heat. LPL activity regulated angiopoietin-like 4 (ANGPTL4), a secretory protein produced tissues (AT), liver, kidney, muscle. While role ANGPTL4 regulating metabolism well established, specific contribution BAT derived controlling lipid glucose...
Hepatic uptake and biosynthesis of fatty acids (FAs), as well the partitioning FAs into oxidative, storage, secretory pathways, are tightly regulated processes. Dysregulation one or more these processes can promote excess hepatic lipid accumulation, ultimately leading to systemic metabolic dysfunction. Angiopoietin-like-4 (ANGPTL4) is a protein that inhibits lipoprotein lipase (LPL) modulates triacylglycerol (TAG) homeostasis. To understand role ANGPTL4 in liver metabolism under normal...
Hypothalamic feeding circuits have been identified as having innate synaptic plasticity, mediating adaption to the changing metabolic milieu by controlling responses and obesity. However, less is known about regulatory principles underlying dynamic changes in agouti-related protein (AgRP) perikarya, a region crucial for gating of neural excitation and, hence, feeding. Here we show that AgRP neurons activated food deprivation, ghrelin administration, or chemogenetics decreased their own...
Abstract AgRP neurons drive hunger, and excessive nutrient intake is the primary driver of obesity associated metabolic disorders. While many factors impacting central regulation feeding behavior have been established, role microRNAs in this process poorly understood. Utilizing unique mouse models, we demonstrate that miR-33 plays a critical neurons, loss leads to increased feeding, obesity, dysfunction mice. These effects include multiple target genes involved mitochondrial biogenesis fatty...
The orexigenic effect of ghrelin is mediated by neuropeptide Y (NPY) and agouti-related protein (AgRP) in the hypothalamic arcuate nucleus (ARC). Recent evidence also indicates that promotes feeding through a mechanism involving activation AMP-activated kinase (AMPK) inactivation acetyl-CoA carboxylase fatty acid synthase (FAS). This results decreased levels malonyl-CoA, increased carnitine palmitoyltransferase 1 (CPT1) activity, mitochondrial production reactive oxygen species. We evaluated...
Evidence suggests that the adipocyte-derived hormone resistin (RSTN) directly regulates both feeding and peripheral metabolism through, so far, undefined hypothalamic-mediated mechanisms. Here, we demonstrate anorectic effect of RSTN is associated with inappropriately decreased mRNA expression orexigenic (agouti-related protein neuropeptide Y) increased anorexigenic (cocaine amphetamine-regulated transcript) neuropeptides in arcuate nucleus hypothalamus. Of interest, also exerts a profound...
GH plays a major role in the regulation of lipid metabolism and alterations axis elicit changes fat distribution mobilization. For example, patients with deficiency (GHD) or mice lacking receptor, percentage is increased. In addition to direct actions on metabolism, current evidence indicates that ghrelin, stomach-derived peptide hormone potent secretagogue action, increases lipogenesis white adipose tissue (WAT) through hypothalamic-mediated mechanism. Still, mechanism by which tone...
Appropriate cristae remodeling is a determinant of mitochondrial function and bioenergetics thus represents crucial process for cellular metabolic adaptations. Here, we show that architecture expression the master cristae-remodeling protein OPA1 in proopiomelanocortin (POMC) neurons, which are key sensors implicated energy balance control, affected by fluctuations nutrient availability. Genetic inactivation POMC neurons causes dramatic alterations topology, Ca2+ handling, reduction...